Skip to main content
SpringerLink
Log in
Book cover

Bone and Cancer pp 19–42Cite as

Genetics of Osteosarcoma

  • Chapter
  • First Online:

  • 1013 Accesses

Part of the book series: Topics in Bone Biology ((TBB,volume 5))

Abstract

Primary malignant tumors of bone are rare and constitute one of the more uncommon types of neoplasms. Only about 1,500 new bone sarcomas are reported in the United States each year. Yet, because of the effects of radical surgery and chemotherapy, the very existence of these tumors leads to a significant reduction in the quality of life in children and adolescents. Notwithstanding their rarity, primary tumors are important for understanding cancer and its treatment.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Abdelwahab IF, Kenan S, Hermann G, and Klein MJ, (1997) Dedifferentiated parosteal osteosarcoma of the radius. Skeletal Radiol 26: 242–245.

    Article  PubMed  CAS  Google Scholar 

  2. Abramovici LC, Hytiroglou P, Klein RM, Karkavelas G, Drevelegas A, Panousi E, and Steiner GC, (2005) Well-differentiated extraskeletal osteosarcoma: report of 2 cases, 1 with dedifferentiation. Hum Pathol 36: 439–443.

    Google Scholar 

  3. Akatsuka T, Wada T, Kokai Y, Kawaguchi S, Isu K, Yamashiro K, Yamashita T, Sawada N, Yamawaki S, and Ishii S, (2002) ErbB2 expression is correlated with increased survival of patients with osteosarcoma. Cancer 94: 1397–1404.

    Article  PubMed  CAS  Google Scholar 

  4. Akatsuka T, Wada T, Kokai Y, Sawada N, Yamawaki S, and Ishii S, (2001) Loss of ErbB2 expression in pulmonary metastatic lesions in osteosarcoma. Oncology 60: 361–366.

    Article  PubMed  CAS  Google Scholar 

  5. Ando T, Ichikawa J, Okamoto A, Tasaka K, Nakao A, and Hamada Y, (2005) Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines. J Orthop Res 23: 964–969.

    Article  PubMed  CAS  Google Scholar 

  6. Anninga JK, van de Vijver MJ, Cleton-Jansen AM, Kristel PM, Taminiau AH, Nooij M, Egeler RM, and Hogendoorn PC, (2004) Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas. Eur J Cancer 40: 963–970.

    Article  PubMed  CAS  Google Scholar 

  7. Araki N, Uchida A, Kimura T, Yoshikawa H, Aoki Y, Ueda T, Takai S, Miki T, and Ono K, (1991) Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors. Clin Orthop Relat Res 271–277.

    Google Scholar 

  8. Atiye J, Wolf M, Kaur S, Monni O, Bohling T, Kivioja A, Tas E, Serra M, Tarkkanen M, and Knuutila S, (2005) Gene amplifications in osteosarcoma – CGH microarray analysis. Genes Chromosomes Cancer 42: 158–163.

    Article  PubMed  CAS  Google Scholar 

  9. Aue G, Muralidhar B, Schwartz HS, and Butler MG, (1998) Telomerase activity in skeletal sarcomas. Ann Surg Oncol 5: 627–634.

    Article  PubMed  CAS  Google Scholar 

  10. Ayala AG, Ro JY, Papadopoulos NK, Raymond AK, and Edeiken J, (1993) Small cell osteosarcoma. Cancer Treat Res 62: 139–149.

    Article  PubMed  CAS  Google Scholar 

  11. Ayala AG, Ro JY, Raymond AK, Jaffe N, Chawla S, Carrasco H, Link M, Jimenez J, Edeiken J, Wallace S et al., (1989) Small cell osteosarcoma. A clinicopathologic study of 27 cases. Cancer 64: 2162–2173.

    Article  PubMed  CAS  Google Scholar 

  12. Bacci G, Briccoli A, Rocca M, Ferrari S, Donati D, Longhi A, Bertoni F, Bacchini P, Giacomini S, Forni C, Manfrini M, and Galletti S, (2003) Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol 14: 1126–1134.

    Article  PubMed  CAS  Google Scholar 

  13. Bacci G, Ferrari S, Ruggieri P, Biagini R, Fabbri N, Campanacci L, Bacchini P, Longhi A, Forni C, and Bertoni F, (2001) Telangiectatic osteosarcoma of the extremity: neoadjuvant chemotherapy in 24 cases. Acta Orthop Scand 72: 167–172.

    Article  PubMed  CAS  Google Scholar 

  14. Bane BL, Evans HL, Ro JY, Carrasco CH, Grignon DJ, Benjamin RS, and Ayala AG, (1990) Extraskeletal osteosarcoma. A clinicopathologic review of 26 cases. Cancer 65: 2762–2770.

    Article  PubMed  CAS  Google Scholar 

  15. Batanian JR, Cavalli LR, Aldosari NM, Ma E, Sotelo-Avila C, Ramos MB, Rone JD, Thorpe CM, and Haddad BR, (2002) Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses. Mol Pathol 55: 389–393.

    Article  PubMed  CAS  Google Scholar 

  16. Beghini A, Castorina P, Roversi G, Modiano P, and Larizza L, (2003) RNA processing defects of the helicase gene RECQL4 in a compound heterozygous Rothmund–Thomson patient. Am J Med Genet A 120: 395–399.

    Article  Google Scholar 

  17. Benassi MS, Molendini L, Gamberi G, Magagnoli G, Ragazzini P, Gobbi GA, Sangiorgi L, Pazzaglia L, Asp J, Brantsing C, and Picci P, (2001) Involvement of INK4A gene products in the pathogenesis and development of human osteosarcoma. Cancer 92: 3062–3067.

    Article  PubMed  CAS  Google Scholar 

  18. Bennett JH, Thomas G, Evans AW, and Speight PM, (2000) Osteosarcoma of the jaws: a 30-year retrospective review. Oral Surg, Oral Med, Oral Pathol, Oral Radiol, Endod 90: 323–332.

    Article  CAS  Google Scholar 

  19. Bertoni F, Bacchini P, and Staals EL, (2003) Giant cell-rich osteosarcoma. Orthopedics 26: 179–181.

    PubMed  Google Scholar 

  20. Bilous M, Dowsett M, Hanna W, Isola J, Lebeau A, Moreno A, Penault-Llorca F, Ruschoff J, Tomasic G, and van de Vijver M, (2003) Current perspectives on HER2 testing: a review of national testing guidelines. Mod Pathol 16: 173–182.

    Article  PubMed  Google Scholar 

  21. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, and Greider CW, (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91: 25–34.

    Article  PubMed  CAS  Google Scholar 

  22. Brehm A and Kouzarides T, (1999) Retinoblastoma protein meets chromatin. Trends Biochem Sci 24: 142–145.

    Article  Google Scholar 

  23. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, and Kouzarides T, (1998) Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391: 597–601.

    Article  PubMed  CAS  Google Scholar 

  24. Briant TD and Bird R, (1981) Osteogenic sarcoma of the mandible. J Otolaryngol 10: 149–161.

    Google Scholar 

  25. Brooks CL and Gu W, (2006) p53 ubiquitination: Mdm2 and beyond. Mol Cell 21: 307-315.

    Article  CAS  Google Scholar 

  26. Casalini P, Iorio MV, Galmozzi E, and Menard S, (2004) Role of HER receptors family in development and differentiation. J Cell Physiol 200: 343–350.

    Article  PubMed  CAS  Google Scholar 

  27. Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, and Gruss P, (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94: 727–737.

    Article  PubMed  CAS  Google Scholar 

  28. Chambers I, (2004) The molecular basis of pluripotency in mouse embryonic stem cells. Cloning Stem Cells 6: 386–391.

    Article  PubMed  CAS  Google Scholar 

  29. Chang S, Khoo CM, Naylor ML, Maser RS, and DePinho RA, (2003) Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Genes Dev 17: 88–100.

    Article  PubMed  CAS  Google Scholar 

  30. Chano T, Matsumoto K, Ishizawa M, Morimoto S, Hukuda S, Okabe H, Kato H, and Fujino S, (1996) Analysis of the presence of osteocalcin, S-100 protein, and proliferating cell nuclear antigen in cells of various types of osteosarcomas. Eur J Histochem 40: 189–198.

    PubMed  CAS  Google Scholar 

  31. Charames GS and Bapat B, (2003) Genomic instability and cancer. Curr Mol Med 3: 589–596.

    Article  Google Scholar 

  32. Chau BN and Wang JY, (2003) Coordinated regulation of life and death by RB. Nat Rev Cancer 3: 130–138.

    Article  CAS  Google Scholar 

  33. Cheung AL and Deng W, (2008) Telomere dysfunction, genome instability and cancer. Front Biosci 13: 2075–2090.

    Article  Google Scholar 

  34. Chou WC, Hawkins AL, Barrett JF, Griffin CA, and Dang CV, (2001) Arsenic inhibition of telomerase transcription leads to genetic instability. J Clin Invest 108: 1541–1547.

    PubMed  CAS  Google Scholar 

  35. Chung EB and Enzinger FM, (1987) Extraskeletal osteosarcoma. Cancer 60: 1132–1142.

    Article  Google Scholar 

  36. Chung UI, Kawaguchi H, Takato T, and Nakamura K, (2004) Distinct osteogenic mechanisms of bones of distinct origins. J Orthop Sci 9: 410–414.

    Article  PubMed  CAS  Google Scholar 

  37. Clark JL, Unni KK, Dahlin DC, and Devine KD, (1983) Osteosarcoma of the jaw. Cancer 51: 2311–2316.

    Article  PubMed  CAS  Google Scholar 

  38. Classon M and Harlow E, (2002) The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2: 910–917.

    Article  CAS  Google Scholar 

  39. Cohen MM, Jr., (2000) Merging the old skeletal biology with the new. I. Intramembranous ossification, endochondral ossification, ectopic bone, secondary cartilage, and pathologic considerations. J Craniofac Genet Dev Biol 20: 84–93.

    Google Scholar 

  40. Cohen S, Ushiro H, Stoscheck C, and Chinkers M, (1982) A native 170,000 epidermal growth factor receptor–kinase complex from shed plasma membrane vesicles. J Biol Chem 257: 1523–1531.

    PubMed  CAS  Google Scholar 

  41. Curran T, MacConnell WP, van Straaten F, and Verma IM, (1983) Structure of the FBJ murine osteosarcoma virus genome: molecular cloning of its associated helper virus and the cellular homolog of the v-fos gene from mouse and human cells. Mol Cell Biol 3: 914–921.

    PubMed  CAS  Google Scholar 

  42. Curran T, Peters G, Van Beveren C, Teich NM, and Verma IM, (1982) FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol 44: 674–682.

    PubMed  CAS  Google Scholar 

  43. Daroszewska A and Ralston SH, (2005) Genetics of Paget’s disease of bone. Clin Sci (Lond) 109: 257–263.

    Article  CAS  Google Scholar 

  44. De Lange T, (2005) Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol 70: 197–204.

    Article  PubMed  Google Scholar 

  45. Deshpande A and Hinds PW, (2006) The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr Mol Med 6: 809–817.

    Google Scholar 

  46. Deshpande A, Sicinski P, and Hinds PW, (2005) Cyclins and cdks in development and cancer: a perspective. Oncogene 24: 2909–2915.

    Article  PubMed  CAS  Google Scholar 

  47. Desmaze C, Soria JC, Freulet-Marriere MA, Mathieu N, and Sabatier L, (2003) Telomere-driven genomic instability in cancer cells. Cancer Lett 194: 173–182.

    Article  PubMed  CAS  Google Scholar 

  48. Diller L, Kassel J, Nelson CE, Gryka MA, Litwak G, Gebhardt M, Bressac B, Ozturk M, Baker SJ, Vogelstein B, et al., (1990) p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 10: 5772–5781.

    PubMed  CAS  Google Scholar 

  49. dos Santos Aguiar S, de Jesus Girotto Zambaldi L, dos Santos AM, Pinto W, Jr., and Brandalise SR, (2007) Comparative genomic hybridization analysis of abnormalities in chromosome 21 in childhood osteosarcoma. Cancer Genet Cytogenet 175: 35-40.

    Article  PubMed  CAS  Google Scholar 

  50. Dryja TP, Rapaport JM, Epstein J, Goorin AM, Weichselbaum R, Koufos A, and Cavenee WK, (1986) Chromosome 13 homozygosity in osteosarcoma without retinoblastoma. Am J Hum Genet 38: 59–66.

    PubMed  CAS  Google Scholar 

  51. Duan X, Jia SF, Koshkina N, and Kleinerman ES, (2006) Intranasal interleukin-12 gene therapy enhanced the activity of ifosfamide against osteosarcoma lung metastases. Cancer 106: 1382–1388.

    Article  PubMed  CAS  Google Scholar 

  52. Duan X, Zhou Z, Jia SF, Colvin M, Lafleur EA, and Kleinerman ES, (2004) Interleukin-12 enhances the sensitivity of human osteosarcoma cells to 4-hydroperoxycyclophosphamide by a mechanism involving the Fas/Fas-ligand pathway. Clin Cancer Res 10: 777–783.

    Article  PubMed  CAS  Google Scholar 

  53. Dubec JJ, Munk PL, O’Connell JX, Lee MJ, Janzen D, Connell D, Masri B, and Logan PM, (1997) Soft tissue osteosarcoma with telangiectatic features: MR imaging findings in two cases. Skeletal Radiol 26: 732–736.

    Article  PubMed  CAS  Google Scholar 

  54. Dyson N, (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12: 2245–2262.

    Article  PubMed  CAS  Google Scholar 

  55. Eames BF, de la Fuente L, and Helms JA, (2003) Molecular ontogeny of the skeleton. Birth Defects Res C Embryo Today 69: 93–101.

    Article  PubMed  CAS  Google Scholar 

  56. Elmore LW, Turner KC, Gollahon LS, Landon MR, Jackson-Cook CK, and Holt SE, (2002) Telomerase protects cancer-prone human cells from chromosomal instability and spontaneous immortalization. Cancer Biol Ther 1: 391–397.

    PubMed  CAS  Google Scholar 

  57. Feldser DM, Hackett JA, and Greider CW, (2003) Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer 3: 623–627.

    Article  PubMed  CAS  Google Scholar 

  58. Fellenberg J, Krauthoff A, Pollandt K, Delling G, and Parsch D, (2004) Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue. Lab Invest 84: 113–121.

    Article  PubMed  CAS  Google Scholar 

  59. Ferguson WS and Goorin AM, (2001) Current treatment of osteosarcoma. Cancer Invest 19: 292–315.

    Article  Google Scholar 

  60. Fernandes R, Nikitakis NG, Pazoki A, and Ord RA, (2007) Osteogenic sarcoma of the jaw: a 10-year experience. J Oral Maxillofac Surg 65: 1286–1291.

    Article  PubMed  Google Scholar 

  61. Feuk L, Carson AR, and Scherer SW, (2006) Structural variation in the human genome. Nat Rev Genet 7: 85-97.

    Article  PubMed  CAS  Google Scholar 

  62. Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, and Geurts van Kessel A, (1995) Comparative genomic hybridization analysis of human sarcomas: II. Identification of novel amplicons at 6p and 17p in osteosarcomas. Genes Chromosomes Cancer 14: 15–21.

    Article  PubMed  CAS  Google Scholar 

  63. Fraser WD, (1997) Paget’s disease of bone. Curr Opin Rheumatol 9: 347–354.

    Article  PubMed  CAS  Google Scholar 

  64. Freydinger JE, Duhig JT, and Mc DL, (1963) Sarcoma complicating Paget’s disease of bone. A study of seven cases with report of one long survival after surgery. Arch Pathol 75: 496–500.

    Google Scholar 

  65. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, and Dryja TP, (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323: 643–646.

    Article  PubMed  CAS  Google Scholar 

  66. Fung YK, Murphree AL, T’Ang A, Qian J, Hinrichs SH, and Benedict WF, (1987) Structural evidence for the authenticity of the human retinoblastoma gene. Science 236: 1657–1661.

    Article  PubMed  CAS  Google Scholar 

  67. Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, and Stratton MR, (2004) A census of human cancer genes. Nat Rev Cancer 4: 177–183.

    Article  PubMed  CAS  Google Scholar 

  68. Gamberi G, Ragazzini P, Benassi MS, Ferrari C, Sollazzo MR, Molendini L, Merli M, Magagnoli G, Ruggieri P, Balladelli A, Orlando C, Bacchini P, Pazzagli M, and Picci P, (2000) Analysis of 12q13–15 genes in parosteal osteosarcoma. Clin Orthop Relat Res 195–204.

    Google Scholar 

  69. Genovese C, Trani D, Caputi M, and Claudio PP, (2006) Cell cycle control and beyond: emerging roles for the retinoblastoma gene family. Oncogene 25: 5201–5209.

    Article  PubMed  CAS  Google Scholar 

  70. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, Scott EW, Ghivizzani SC, Ignatova TN, and Steindler DA, (2005) Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia 7: 967–976.

    Article  PubMed  CAS  Google Scholar 

  71. Gilmore AP, Valentijn AJ, Wang P, Ranger AM, Bundred N, O’Hare MJ, Wakeling A, Korsmeyer SJ, and Streuli CH, (2002) Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem 277: 27643–27650.

    Article  PubMed  CAS  Google Scholar 

  72. Gisselsson D, Jonson T, Petersen A, Strombeck B, Dal Cin P, Hoglund M, Mitelman F, Mertens F, and Mandahl N, (2001) Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proc Natl Acad Sci USA 98: 12683–12688.

    Article  PubMed  CAS  Google Scholar 

  73. Glass DA, 2nd and Karsenty G, (2006) Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. Curr Top Dev Biol 73: 43–84.

    Article  PubMed  CAS  Google Scholar 

  74. Glass DA, 2nd and Karsenty G, (2007) In vivo analysis of Wnt signaling in bone. Endocrinology 148: 2630–2634.

    Article  PubMed  CAS  Google Scholar 

  75. Gollin SM, (2004) Chromosomal instability. Curr Opin Oncol 16: 25–31.

    Article  PubMed  Google Scholar 

  76. Goralczyk R, Closs EI, Ruther U, Wagner EF, Strauss PG, Erfle V, and Schmidt J, (1990) Characterization of fos-induced osteogenic tumours and tumour-derived murine cell lines. Differentiation 44: 122–131.

    Article  PubMed  CAS  Google Scholar 

  77. Gordon N, Arndt CA, Hawkins DS, Doherty DK, Inwards CY, Munsell MF, Stewart J, Koshkina NV, and Kleinerman ES, (2005) Fas expression in lung metastasis from osteosarcoma patients. J Pediatr Hematol Oncol 27: 611–615.

    Article  PubMed  Google Scholar 

  78. Gordon N, Koshkina NV, Jia SF, Khanna C, Mendoza A, Worth LL, and Kleinerman ES, (2007) Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine. Clin Cancer Res 13: 4503–4510.

    Article  PubMed  CAS  Google Scholar 

  79. Gorlick R, Huvos AG, Heller G, Aledo A, Beardsley GP, Healey JH, and Meyers PA, (1999) Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17: 2781–2788.

    PubMed  CAS  Google Scholar 

  80. Goto M, Miller RW, Ishikawa Y, and Sugano H, (1996) Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 5: 239–246.

    PubMed  CAS  Google Scholar 

  81. Graus-Porta D, Beerli RR, Daly JM, and Hynes NE, (1997) ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. Embo J 16: 1647–1655.

    Article  PubMed  CAS  Google Scholar 

  82. Greditzer HG, 3rd, McLeod RA, Unni KK, and Beabout JW, (1983) Bone sarcomas in Paget’s disease. Radiology 146: 327–333.

    PubMed  Google Scholar 

  83. Gregory CA, Singh H, Perry AS, and Prockop DJ, (2003) The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem 278: 28067–28078.

    Article  PubMed  CAS  Google Scholar 

  84. Grigoriadis AE, Schellander K, Wang ZQ, and Wagner EF, (1993) Osteoblasts are target cells for transformation in c-fos transgenic mice. J Cell Biol 122: 685–701.

    Article  PubMed  CAS  Google Scholar 

  85. Grimer RJ, Bielack S, Flege S, Cannon SR, Foleras G, Andreeff I, Sokolov T, Taminiau A, Dominkus M, San-Julian M, Kollender Y, and Gosheger G, (2005) Periosteal osteosarcoma–a European review of outcome. Eur J Cancer 41: 2806–2811.

    Article  PubMed  Google Scholar 

  86. Guo Y, Zi X, Koontz Z, Kim A, Xie J, Gorlick R, Holcombe RF, and Hoang BH, (2007) Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells. J Orthop Res 25: 964–971.

    Article  PubMed  CAS  Google Scholar 

  87. Guo Z, Yikang S, Yoshida H, Mak TW, and Zacksenhaus E, (2001) Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease-activating factor-1 dependent and independent apoptotic pathways during embryogenesis. Cancer Res 61: 8395–8400.

    PubMed  CAS  Google Scholar 

  88. Hackett JA, Feldser DM, and Greider CW, (2001) Telomere dysfunction increases mutation rate and genomic instability. Cell 106: 275–286.

    Article  PubMed  CAS  Google Scholar 

  89. Hackett JA and Greider CW, (2002) Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis. Oncogene 21: 619–626.

    Article  Google Scholar 

  90. Haddy TB, Mosher RB, Dinndorf PA, and Reaman GH, (2004) Second neoplasms in survivors of childhood and adolescent cancer are often treatable. J Adolesc Health 34: 324–329.

    PubMed  Google Scholar 

  91. Hadjipavlou A, Lander P, Srolovitz H, and Enker IP, (1992) Malignant transformation in Paget’s disease of bone. Cancer 70: 2802–2808.

    Article  PubMed  CAS  Google Scholar 

  92. Haibach H, Farrell C, and Dittrich FJ, (1985) Neoplasms arising in Paget’s disease of bone: a study of 82 cases. Am J Clin Pathol 83: 594–600.

    PubMed  CAS  Google Scholar 

  93. Hall FM, (1983) Incidence of bone sarcoma in Paget’s disease. Radiology 148: 865.

    PubMed  CAS  Google Scholar 

  94. Hall RB, Robinson LH, Malawar MM, and Dunham WK, (1985) Periosteal osteosarcoma. Cancer 55: 165–171.

    Article  PubMed  CAS  Google Scholar 

  95. Hanada K and Hickson ID, (2007) Molecular genetics of RecQ helicase disorders. Cell Mol Life Sci 64: 2306–2322.

    Article  CAS  Google Scholar 

  96. Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Brogger A, Gedde-Dahl T, and Cavenee WK, (1985) Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA 82: 6216–6220.

    Article  PubMed  CAS  Google Scholar 

  97. Hansen MF, Nellissery MJ, and Bhatia P, (1999) Common mechanisms of osteosarcoma and Paget’s disease. J Bone Miner Res 14 Suppl 2: 39–44.

    Article  PubMed  Google Scholar 

  98. Harbour JW and Dean DC, (2000) Chromatin remodeling and Rb activity. Curr Opin Cell Biol 12: 685–689.

    Article  Google Scholar 

  99. Harbour JW and Dean DC, (2000) Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2: E65–67.

    Article  CAS  Google Scholar 

  100. Harbour JW and Dean DC, (2001) Corepressors and retinoblastoma protein function. Curr Top Microbiol Immunol 254: 137–144.

    Google Scholar 

  101. Harris SL and Levine AJ, (2005) The p53 pathway: positive and negative feedback loops. Oncogene 24: 2899–2908.

    Article  CAS  Google Scholar 

  102. Hartley AL, Birch JM, Marsden HB, and Harris M, (1986) Breast cancer risk in mothers of children with osteosarcoma and chondrosarcoma. Br J Cancer 54: 819–823.

    Article  PubMed  CAS  Google Scholar 

  103. Hattinger CM, Reverter-Branchat G, Remondini D, Castellani GC, Benini S, Pasello M, Manara MC, Scotlandi K, Picci P, and Serra M, (2003) Genomic imbalances associated with methotrexate resistance in human osteosarcoma cell lines detected by comparative genomic hybridization-based techniques. Eur J Cell Biol 82: 483–493.

    Article  PubMed  CAS  Google Scholar 

  104. Hemann MT, Strong MA, Hao LY, and Greider CW, (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107: 67–77.

    Article  PubMed  CAS  Google Scholar 

  105. Henson JD, Neumann AA, Yeager TR, and Reddel RR, (2002) Alternative lengthening of telomeres in mammalian cells. Oncogene 21: 598–610.

    Article  PubMed  CAS  Google Scholar 

  106. Herbst RS, (2004) Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 59: 21–26.

    Article  PubMed  CAS  Google Scholar 

  107. Hickman ES, Moroni MC, and Helin K, (2002) The role of p53 and pRB in apoptosis and cancer. Curr Opin Genet Dev 12: 60–66.

    Article  PubMed  CAS  Google Scholar 

  108. Hickson ID, (2003) RecQ helicases: caretakers of the genome. Nat Rev Cancer 3: 169–178.

    Article  PubMed  CAS  Google Scholar 

  109. Hoang BH, Kubo T, Healey JH, Sowers R, Mazza B, Yang R, Huvos AG, Meyers PA, and Gorlick R, (2004) Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer 109: 106–111.

    Article  PubMed  CAS  Google Scholar 

  110. Hoang BH, Kubo T, Healey JH, Yang R, Nathan SS, Kolb EA, Mazza B, Meyers PA, and Gorlick R, (2004) Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Cancer Res 64: 2734–2739.

    Article  PubMed  CAS  Google Scholar 

  111. Holbro T, Civenni G, and Hynes NE, (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284: 99–110.

    Article  PubMed  CAS  Google Scholar 

  112. Hoogerwerf WA, Hawkins AL, Perlman EJ, and Griffin CA, (1994) Chromosome analysis of nine osteosarcomas. Genes Chromosomes Cancer 9: 88–92.

    Article  PubMed  CAS  Google Scholar 

  113. Hoshi M, Matsumoto S, Manabe J, Tanizawa T, Shigemitsu T, Takeuchi K, and Kawaguchi N, (2006) Report of four cases with high-grade surface osteosarcoma. Jpn J Clin Oncol 36: 180–184.

    Google Scholar 

  114. Huang HJ, Yee JK, Shew JY, Chen PL, Bookstein R, Friedmann T, Lee EY, and Lee WH, (1988) Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 242: 1563–1566.

    Article  PubMed  CAS  Google Scholar 

  115. Hughes DP, Thomas DG, Giordano TJ, Baker LH, and McDonagh KT, (2004) Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma. Cancer Res 64: 2047–2053.

    Article  PubMed  CAS  Google Scholar 

  116. Hughes SC and Fehon RG, (2007) Understanding ERM proteins–the awesome power of genetics finally brought to bear. Curr Opin Cell Biol 19: 51–56.

    Article  CAS  Google Scholar 

  117. Huvos AG, (1986) Osteogenic sarcoma of bones and soft tissues in older persons. A clinicopathologic analysis of 117 patients older than 60 years. Cancer 57: 1442–1449.

    Article  PubMed  CAS  Google Scholar 

  118. Huvos AG, Butler A, and Bretsky SS, (1983) Osteogenic sarcoma associated with Paget’s disease of bone. A clinicopathologic study of 65 patients. Cancer 52: 1489–1495.

    Article  PubMed  CAS  Google Scholar 

  119. Hynes NE, Horsch K, Olayioye MA, and Badache A, (2001) The ErbB receptor tyrosine family as signal integrators. Endocr Relat Cancer 8: 151–159.

    Article  PubMed  CAS  Google Scholar 

  120. Isfort RJ, Cody DB, Lovell G, and Doersen CJ, (1995) Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. Mol Carcinog 14: 170–178.

    Article  PubMed  CAS  Google Scholar 

  121. Issing WJ, Wustrow TP, Oeckler R, Mezger J, and Nerlich A, (1993) An association of the RB gene with osteosarcoma: molecular genetic evaluation of a case of hereditary retinoblastoma. Eur Arch Otorhinolaryngol 250: 277-280.

    PubMed  CAS  Google Scholar 

  122. Iwakuma T and Lozano G, (2003) MDM2, an introduction. Mol Cancer Res 1: 993–1000.

    Google Scholar 

  123. Jasnau S, Meyer U, Potratz J, Jundt G, Kevric M, Joos UK, Jurgens H, and Bielack SS, (2008) Craniofacial osteosarcoma experience of the cooperative German-Austrian-Swiss osteosarcoma study group. Oral Oncol 44: 286–294.

    Google Scholar 

  124. Jia SF, Worth LL, Turan M, Duan Xp XP, and Kleinerman ES, (2002) Eradication of osteosarcoma lung metastasis using intranasal gemcitabine. Anticancer Drugs 13: 155–161.

    Article  PubMed  CAS  Google Scholar 

  125. Johnson JE and Broccoli D, (2007) Telomere maintenance in sarcomas. Curr Opin Oncol 19: 377–382.

    Article  Google Scholar 

  126. Johnson-Pais TL, Nellissery MJ, Ammerman DG, Pathmanathan D, Bhatia P, Buller CL, Leach RJ, and Hansen MF, (2003) Determination of a minimal region of loss of heterozygosity on chromosome 18q21.33 in osteosarcoma. Int J Cancer 105: 285–288.

    Article  PubMed  CAS  Google Scholar 

  127. Junior AT, de Abreu Alves F, Pinto CA, Carvalho AL, Kowalski LP, and Lopes MA, (2003) Clinicopathological and immunohistochemical analysis of twenty-five head and neck osteosarcomas. Oral Oncol 39: 521–530.

    Article  PubMed  CAS  Google Scholar 

  128. Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, Kotz R, Salzer-Kuntschik M, Winkelmann W, Jundt G, Kabisch H, Reichardt P, Jurgens H, Gadner H, and Bielack SS, (2003) Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 21: 2011–2018.

    Article  PubMed  Google Scholar 

  129. Kallioniemi OP, Kallioniemi A, Kurisu W, Thor A, Chen LC, Smith HS, Waldman FM, Pinkel D, and Gray JW, (1992) ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci USA 89: 5321–5325.

    Article  PubMed  CAS  Google Scholar 

  130. Kanoe H, Nakayama T, Murakami H, Hosaka T, Yamamoto H, Nakashima Y, Tsuboyama T, Nakamura T, Sasaki MS, and Toguchida J, (1998) Amplification of the CDK4 gene in sarcomas: tumor specificity and relationship with the RB gene mutation. Anticancer Res 18: 2317–2321.

    PubMed  CAS  Google Scholar 

  131. Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ, Weber RJ, Haussler D, and Kent WJ, (2003) The UCSC genome browser database. Nucleic Acids Res 31: 51–54.

    Article  PubMed  CAS  Google Scholar 

  132. Kaste SC, Fuller CE, Saharia A, Neel MD, Rao BN, and Daw NC, (2006) Pediatric surface osteosarcoma: clinical, pathologic, and radiologic features. Pediatr Blood Cancer 47: 152–162.

    Article  PubMed  Google Scholar 

  133. Kaur S, Larramendy ML, Vauhkonen H, Bohling T, and Knuutila S, (2007) Loss of TP53 in sarcomas with 17p12 to approximately p11 gain. A fine-resolution oligonucleotide array comparative genomic hybridization study. Cytogenet Genome Res 116: 153–157.

    CAS  Google Scholar 

  134. Kawaguchi K, Oda Y, Sakamoto A, Saito T, Tamiya S, Iwamoto Y, and Tsuneyoshi M, (2002) Molecular analysis of p53, MDM2, and H-ras genes in osteosarcoma and malignant fibrous histiocytoma of bone in patients older than 40 years. Mod Pathol 15: 878–888.

    Article  PubMed  Google Scholar 

  135. Khanna C, Khan J, Nguyen P, Prehn J, Caylor J, Yeung C, Trepel J, Meltzer P, and Helman L, (2001) Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer Res 61: 3750–3759.

    PubMed  CAS  Google Scholar 

  136. Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM, and Helman LJ, (2004) The membrane–cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med 10: 182–186.

    Article  PubMed  CAS  Google Scholar 

  137. Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ, and Look AT, (1993) Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res 53: 5535–5541.

    PubMed  CAS  Google Scholar 

  138. Kido A, Schneider-Stock R, Hauptmann K, and Roessner A, (2003) Telomerase activity in juxtacortical and conventional high-grade osteosarcomas: correlation with grade, proliferative activity and clinical response to chemotherapy. Cancer Lett 196: 109–115.

    Article  PubMed  CAS  Google Scholar 

  139. Kilpatrick SE, Geisinger KR, King TS, Sciarrotta J, Ward WG, Gold SH, and Bos GD, (2001) Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 14: 1277–1283.

    Article  PubMed  CAS  Google Scholar 

  140. Kim MS, Song WS, Cho WH, Lee SY, and Jeon DG, (2007) Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res 459: 229–236.

    Article  PubMed  Google Scholar 

  141. Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, and Furuichi Y, (1999) Mutations in RECQL4 cause a subset of cases of Rothmund–Thomson syndrome. Nat Genet 22: 82–84.

    Article  PubMed  CAS  Google Scholar 

  142. Kitchin FD and Ellsworth RM, (1974) Pleiotropic effects of the gene for retinoblastoma. J Med Genet 11: 244–246.

    Article  Google Scholar 

  143. Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, and Yarden Y, (1999) The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci USA 96: 4995–5000.

    Article  PubMed  CAS  Google Scholar 

  144. Knudsen ES, Sexton CR, and Mayhew CN, (2006) Role of the retinoblastoma tumor suppressor in the maintenance of genome integrity. Curr Mol Med 6: 749–757.

    PubMed  CAS  Google Scholar 

  145. Knudsen KE, Booth D, Naderi S, Sever-Chroneos Z, Fribourg AF, Hunton IC, Feramisco JR, Wang JY, and Knudsen ES, (2000) RB-dependent S-phase response to DNA damage. Mol Cell Biol 20: 7751–7763.

    Article  PubMed  CAS  Google Scholar 

  146. Kolodner RD, Putnam CD, and Myung K, (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297: 552–557.

    Article  PubMed  CAS  Google Scholar 

  147. Kops GJ, Weaver BA, and Cleveland DW, (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5: 773–785.

    Article  PubMed  CAS  Google Scholar 

  148. Korenjak M and Brehm A, (2005) E2F–Rb complexes regulating transcription of genes important for differentiation and development. Curr Opin Genet Dev 15: 520–527.

    Article  CAS  Google Scholar 

  149. Koshkina NV, Khanna C, Mendoza A, Guan H, DeLauter L, and Kleinerman ES, (2007) Fas-negative osteosarcoma tumor cells are selected during metastasis to the lungs: the role of the Fas pathway in the metastatic process of osteosarcoma. Mol Cancer Res 5: 991–999.

    Article  PubMed  CAS  Google Scholar 

  150. Koshkina NV and Kleinerman ES, (2005) Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases. Int J Cancer 116: 458–463.

    Article  CAS  Google Scholar 

  151. Kramer K, Hicks DG, Palis J, Rosier RN, Oppenheimer J, Fallon MD, and Cohen HJ, (1993) Epithelioid osteosarcoma of bone. Immunocytochemical evidence suggesting divergent epithelial and mesenchymal differentiation in a primary osseous neoplasm. Cancer 71: 2977–2982.

    CAS  Google Scholar 

  152. La Quaglia MP, (1998) Osteosarcoma. Specific tumor management and results. Chest Surg Clin N Am 8: 77–95.

    Google Scholar 

  153. Lafleur EA, Koshkina NV, Stewart J, Jia SF, Worth LL, Duan X, and Kleinerman ES, (2004) Increased Fas expression reduces the metastatic potential of human osteosarcoma cells. Clin Cancer Res 10: 8114–8119.

    Article  PubMed  CAS  Google Scholar 

  154. Lamovec J, Zidar A, Bracko M, and Golouh R, (1994) Primary bone sarcoma with rhabdomyosarcomatous component. Pathol Res Pract 190: 51–60.

    Article  PubMed  CAS  Google Scholar 

  155. Larizza L, Magnani I, and Roversi G, (2006) Rothmund–Thomson syndrome and RECQL4 defect: splitting and lumping. Cancer Lett 232: 107–120.

    Article  PubMed  CAS  Google Scholar 

  156. Lau CC, Harris CP, Lu XY, Perlaky L, Gogineni S, Chintagumpala M, Hicks J, Johnson ME, Davino NA, Huvos AG, Meyers PA, Healy JH, Gorlick R, and Rao PH, (2004) Frequent amplification and rearrangement of chromosomal bands 6p12–p21 and 17p11.2 in osteosarcoma. Genes Chromosomes Cancer 39: 11–21.

    Article  PubMed  Google Scholar 

  157. Lee JS, Fetsch JF, Wasdhal DA, Lee BP, Pritchard DJ, and Nascimento AG, (1995) A review of 40 patients with extraskeletal osteosarcoma. Cancer 76: 2253–2259.

    Article  PubMed  CAS  Google Scholar 

  158. Lee N, Smolarz AJ, Olson S, David O, Reiser J, Kutner R, Daw NC, Prockop DJ, Horwitz EM, and Gregory CA, (2007) A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. Br J Cancer 97: 1552–1559.

    Google Scholar 

  159. Lee SB, Kim SH, Bell DW, Wahrer DC, Schiripo TA, Jorczak MM, Sgroi DC, Garber JE, Li FP, Nichols KE, Varley JM, Godwin AK, Shannon KM, Harlow E, and Haber DA, (2001) Destabilization of CHK2 by a missense mutation associated with Li–Fraumeni Syndrome. Cancer Res 61: 8062–8067.

    PubMed  CAS  Google Scholar 

  160. Lee WH, Bookstein R, Hong F, Young LJ, Shew JY, and Lee EY, (1987) Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235: 1394–1399.

    Article  PubMed  CAS  Google Scholar 

  161. Leonard P, Sharp T, Henderson S, Hewitt D, Pringle J, Sandison A, Goodship A, Whelan J, and Boshoff C, (2003) Gene expression array profile of human osteosarcoma. Br J Cancer 89: 2284–2288.

    Article  PubMed  CAS  Google Scholar 

  162. Li FP and Fraumeni JF, Jr., (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71: 747–752.

    Google Scholar 

  163. Li FP, Fraumeni JF, Jr., Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, and Miller RW, (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48: 5358–5362.

    PubMed  CAS  Google Scholar 

  164. Lidang JM, Schumacher B, Myhre JO, Steen NO, and Keller J, (1998) Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases. Am J Surg Pathol 22: 588–594.

    Article  Google Scholar 

  165. Lim G, Karaskova J, Vukovic B, Bayani J, Beheshti B, Bernardini M, Squire JA, and Zielenska M, (2004) Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63. Cancer Genet Cytogenet 153: 158–164.

    Article  PubMed  CAS  Google Scholar 

  166. Lindell MM, Jr., Shirkhoda A, Raymond AK, Murray JA, and Harle TS, (1987) Parosteal osteosarcoma: radiologic–pathologic correlation with emphasis on CT. AJR Am J Roentgenol 148: 323–328.

    PubMed  Google Scholar 

  167. Lindor NM, Furuichi Y, Kitao S, Shimamoto A, Arndt C, and Jalal S, (2000) Rothmund–Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome. Am J Med Genet 90: 223–228.

    Google Scholar 

  168. Lipinski MM and Jacks T, (1999) The retinoblastoma gene family in differentiation and development. Oncogene 18: 7873–7882.

    Article  CAS  Google Scholar 

  169. Loeb LA, Springgate CF, and Battula N, (1974) Errors in DNA replication as a basis of malignant changes. Cancer Res 34: 2311–2321.

    PubMed  CAS  Google Scholar 

  170. Lopez-Guerrero JA, Lopez-Gines C, Pellin A, Carda C, and Llombart-Bosch A, (2004) Deregulation of the G1 to S-phase cell cycle checkpoint is involved in the pathogenesis of human osteosarcoma. Diagn Mol Pathol 13: 81–91.

    Article  PubMed  Google Scholar 

  171. Maitra A, Wanzer D, Weinberg AG, and Ashfaq R, (2001) Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas. Cancer 92: 677-683.

    Article  PubMed  CAS  Google Scholar 

  172. Malkin D, Li FP, Strong LC, Fraumeni JF, Jr., Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA et al., (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238.

    Article  PubMed  CAS  Google Scholar 

  173. Man TK, Chintagumpala M, Visvanathan J, Shen J, Perlaky L, Hicks J, Johnson M, Davino N, Murray J, Helman L, Meyer W, Triche T, Wong KK, and Lau CC, (2005) Expression profiles of osteosarcoma that can predict response to chemotherapy. Cancer Res 65: 8142–8150.

    Article  PubMed  CAS  Google Scholar 

  174. Man TK, Lu XY, Jaeweon K, Perlaky L, Harris CP, Shah S, Ladanyi M, Gorlick R, Lau CC, and Rao PH, (2004) Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma. BMC Cancer 4: 45.

    Article  PubMed  CAS  Google Scholar 

  175. Mandal D, Srivastava A, Mahlum E, Desai D, Maran A, Yaszemski M, Jalal SM, Gitelis S, Bertoni F, Damron T, Irwin R, O’Connor M, Schwartz H, Bolander ME, and Sarkar G, (2007) Severe suppression of Frzb/sFRP3 transcription in osteogenic sarcoma. Gene 386: 131–138.

    Article  PubMed  CAS  Google Scholar 

  176. Mann MB, Hodges CA, Barnes E, Vogel H, Hassold TJ, and Luo G, (2005) Defective sister-chromatid cohesion, aneuploidy and cancer predisposition in a mouse model of type II Rothmund–Thomson syndrome. Hum Mol Genet 14: 813–825.

    Article  PubMed  CAS  Google Scholar 

  177. Marcial-Seoane RA, Marcial-Seoane MA, Davila-Toro FJ, and Marcial-Rojas RA, (1990) Bone tumors of mixed origin: osteo-liposarcoma and osteo-rhabdomyosarcoma. Bol Asoc Med P R 82: 378–393.

    PubMed  CAS  Google Scholar 

  178. Mardinger O, Givol N, Talmi YP, and Taicher S, (2001) Osteosarcoma of the jaw: The Chaim Sheba Medical Center experience. Oral Surg, Oral Med, Oral Pathol, Oral Radiol, Endod 91: 445–451.

    Article  CAS  Google Scholar 

  179. Marx J, (2002) Debate surges over the origins of genomic defects in cancer. Science 297: 544–546.

    Article  PubMed  CAS  Google Scholar 

  180. Maser RS and DePinho RA, (2002) Connecting chromosomes, crisis, and cancer. Science 297: 565–569.

    Article  Google Scholar 

  181. Masuda H, Miller C, Koeffler HP, Battifora H, and Cline MJ, (1987) Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci USA 84: 7716–7719.

    Article  PubMed  CAS  Google Scholar 

  182. McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, and Jacks T, (1998) Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 12: 1121–1133.

    Article  PubMed  CAS  Google Scholar 

  183. McHugh JB, Thomas DG, Herman JM, Ray ME, Baker LH, Adsay NV, Rabah R, and Lucas DR, (2006) Primary versus radiation-associated craniofacial osteosarcoma: Biologic and clinicopathologic comparisons. Cancer 107: 554–562.

    Article  PubMed  Google Scholar 

  184. McNairn JD, Damron TA, Landas SK, Ambrose JL, and Shrimpton AE, (2001) Inheritance of osteosarcoma and Paget’s disease of bone: a familial loss of heterozygosity study. J Mol Diagn 3: 171-177.

    Article  PubMed  CAS  Google Scholar 

  185. Mervak TR, Unni KK, Pritchard DJ, and McLeod RA, (1991) Telangiectatic osteosarcoma. Clin Orthop Relat Res 135–139.

    Google Scholar 

  186. Meyers PA and Gorlick R, (1997) Osteosarcoma. Pediatr Clin North Am 44: 973–989.

    Article  Google Scholar 

  187. Miller AD, Curran T, and Verma IM, (1984) c-fos protein can induce cellular transformation: a novel mechanism of activation of a cellular oncogene. Cell 36: 51–60.

    Article  PubMed  CAS  Google Scholar 

  188. Miller CW, Aslo A, Campbell MJ, Kawamata N, Lampkin BC, and Koeffler HP, (1996) Alterations of the p15, p16,and p18 genes in osteosarcoma. Cancer Genet Cytogenet 86: 136–142.

    Article  PubMed  CAS  Google Scholar 

  189. Miller CW, Aslo A, Tsay C, Slamon D, Ishizaki K, Toguchida J, Yamamuro T, Lampkin B, and Koeffler HP, (1990) Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer Res 50: 7950–7954.

    PubMed  CAS  Google Scholar 

  190. Miller CW, Aslo A, Won A, Tan M, Lampkin B, and Koeffler HP, (1996) Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol 122: 559–565.

    Article  PubMed  CAS  Google Scholar 

  191. Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, and Koeffler HP, (2002) Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. Genes Chromosomes Cancer 33: 17–21.

    Article  PubMed  CAS  Google Scholar 

  192. Mintz MB, Sowers R, Brown KM, Hilmer SC, Mazza B, Huvos AG, Meyers PA, Lafleur B, McDonough WS, Henry MM, Ramsey KE, Antonescu CR, Chen W, Healey JH, Daluski A, Berens ME, Macdonald TJ, Gorlick R, and Stephan DA, (2005) An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Cancer Res 65: 1748–1754.

    Article  PubMed  CAS  Google Scholar 

  193. Moore TE, King AR, Kathol MH, el-Khoury GY, Palmer R, and Downey PR, (1991) Sarcoma in Paget’s disease of bone: clinical, radiologic, and pathologic features in 22 cases. AJR Am J Roentgenol 156: 1199–1203.

    PubMed  CAS  Google Scholar 

  194. Mori K, Berreur M, Blanchard F, Chevalier C, Guisle-Marsollier I, Masson M, Redini F, and Heymann D, (2007) Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol Rep 18: 1365–1371.

    PubMed  CAS  Google Scholar 

  195. Moroni MC, Hickman ES, Lazzerini Denchi E, Caprara G, Colli E, Cecconi F, Muller H, and Helin K, (2001) Apaf-1 is a transcriptional target for E2F and p53. Nat Cell Biol 3: 552–558.

    Article  PubMed  CAS  Google Scholar 

  196. Mrad K, Sassi S, Smida M, Oubiche F, Mekni A, and Romdhane KB, (2004) Osteosarcoma with rhabdomyosarcomatous component or so-called malignant mesenchymoma of bone. Pathologica 96: 475–478.

    PubMed  CAS  Google Scholar 

  197. Murata H, Kusuzaki K, Hirasawa Y, Ashihara T, Abe T, and Inazawa J, (1999) Relationship between chromosomal aberrations by fluorescence in situ hybridization and DNA ploidy by cytofluorometry in osteosarcoma. Cancer Lett 139: 221–226.

    Article  PubMed  CAS  Google Scholar 

  198. Murata K, Hatamochi A, Shinkai H, Ishikawa Y, Kawaguchi N, and Goto M, (1999) A case of Werner’s syndrome associated with osteosarcoma. J Dermatol 26: 682–686.

    PubMed  CAS  Google Scholar 

  199. Murphey MD, Robbin MR, McRae GA, Flemming DJ, Temple HT, and Kransdorf MJ, (1997) The many faces of osteosarcoma. Radiographics 17: 1205–1231.

    PubMed  CAS  Google Scholar 

  200. Murphey MD, wan Jaovisidha S, Temple HT, Gannon FH, Jelinek JS, and Malawer MM, (2003) Telangiectatic osteosarcoma: radiologic–pathologic comparison. Radiology 229: 545–553.

    Article  PubMed  Google Scholar 

  201. Nagata S, Nishimura H, Uchida M, Hayabuchi N, Zenmyou M, and Harada H, (2006) Giant cell-rich osteosarcoma of the distal femur: radiographic and magnetic resonance imaging findings. Radiat Med 24: 228–232.

    Article  PubMed  Google Scholar 

  202. Nakajima H, Sim FH, Bond JR, and Unni KK, (1997) Small cell osteosarcoma of bone. Review of 72 cases. Cancer 79: 2095–2106.

    Article  PubMed  CAS  Google Scholar 

  203. Nakano T, Tani M, Ishibashi Y, Kimura K, Park YB, Imaizumi N, Tsuda H, Aoyagi K, Sasaki H, Ohwada S, and Yokota J, (2003) Biological properties and gene expression associated with metastatic potential of human osteosarcoma. Clin Exp Metastasis 20: 665–674.

    Article  PubMed  CAS  Google Scholar 

  204. Nakashima H, Nishida Y, Sugiura H, Katagiri H, Yonekawa M, Yamada Y, Iwata H, Nagasaka T, and Ishiguro N, (2003) Telomerase, p53 and PCNA activity in osteosarcoma. Eur J Surg Oncol 29: 564–567.

    Article  PubMed  CAS  Google Scholar 

  205. Nakayama H, (2002) RecQ family helicases: roles as tumor suppressor proteins. Oncogene 21: 9008–9021.

    Article  PubMed  CAS  Google Scholar 

  206. Nakayama T, Toguchida J, Wadayama B, Kanoe H, Kotoura Y, and Sasaki MS, (1995) MDM2 gene amplification in bone and soft-tissue tumors: association with tumor progression in differentiated adipose-tissue tumors. Int J Cancer 64: 342–346.

    Article  PubMed  CAS  Google Scholar 

  207. Nellissery MJ, Padalecki SS, Brkanac Z, Singer FR, Roodman GD, Unni KK, Leach RJ, and Hansen MF, (1998) Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget’s disease of bone. Am J Hum Genet 63: 817–824.

    Article  PubMed  CAS  Google Scholar 

  208. Neve RM, Holbro T, and Hynes NE, (2002) Distinct roles for phosphoinositide 3-kinase, mitogen-activated protein kinase and p38 MAPK in mediating cell cycle progression of breast cancer cells. Oncogene 21: 4567–4576.

    Article  PubMed  CAS  Google Scholar 

  209. Neve RM, Lane HA, and Hynes NE, (2001) The role of overexpressed HER2 in transformation. Ann Oncol 12 Suppl 1: S9–13.

    Article  Google Scholar 

  210. Nevins JR, (2001) The Rb/E2F pathway and cancer. Hum Mol Genet 10: 699–703.

    Article  PubMed  CAS  Google Scholar 

  211. Niehrs C, (2006) Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25: 7469–7481.

    Article  PubMed  CAS  Google Scholar 

  212. Nielsen GP, Burns KL, Rosenberg AE, and Louis DN, (1998) CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. Am J Pathol 153: 159–163.

    Article  PubMed  CAS  Google Scholar 

  213. Nishijo K, Nakayama T, Aoyama T, Okamoto T, Ishibe T, Yasura K, Shima Y, Shibata KR, Tsuboyama T, Nakamura T, and Toguchida J, (2004) Mutation analysis of the RECQL4 gene in sporadic osteosarcomas. Int J Cancer 111: 367–372.

    Article  PubMed  CAS  Google Scholar 

  214. Nowak MA, Komarova NL, Sengupta A, Jallepalli PV, Shih Ie M, Vogelstein B, and Lengauer C, (2002) The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA 99: 16226–16231.

    Article  PubMed  CAS  Google Scholar 

  215. Ochi K, Daigo Y, Katagiri T, Nagayama S, Tsunoda T, Myoui A, Naka N, Araki N, Kudawara I, Ieguchi M, Toyama Y, Toguchida J, Yoshikawa H, and Nakamura Y, (2004) Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles. Int J Oncol 24: 647–655.

    PubMed  CAS  Google Scholar 

  216. Oda D, Bavisotto LM, Schmidt RA, McNutt M, Bruckner JD, Conrad EU, 3rd, and Weymuller EA, Jr., (1997) Head and neck osteosarcoma at the University of Washington. Head Neck 19: 513–523.

    Article  PubMed  CAS  Google Scholar 

  217. Ohata N, Ito S, Yoshida A, Kunisada T, Numoto K, Jitsumori Y, Kanzaki H, Ozaki T, Shimizu K, and Ouchida M, (2006) Highly frequent allelic loss of chromosome 6q16–23 in osteosarcoma: involvement of cyclin C in osteosarcoma. Int J Mol Med 18: 1153–1158.

    PubMed  CAS  Google Scholar 

  218. Okada K, Frassica FJ, Sim FH, Beabout JW, Bond JR, and Unni KK, (1994) Parosteal osteosarcoma. A clinicopathological study. J Bone Joint Surg Am 76: 366–378.

    CAS  Google Scholar 

  219. Okada K, Unni KK, Swee RG, and Sim FH, (1999) High grade surface osteosarcoma: a clinicopathologic study of 46 cases. Cancer 85: 1044–1054.

    Article  PubMed  CAS  Google Scholar 

  220. Olayioye MA, Graus-Porta D, Beerli RR, Rohrer J, Gay B, and Hynes NE, (1998) ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner. Mol Cell Biol 18: 5042–5051.

    PubMed  CAS  Google Scholar 

  221. Olayioye MA, Neve RM, Lane HA, and Hynes NE, (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. Embo J 19: 3159–3167.

    Article  PubMed  CAS  Google Scholar 

  222. Oliner JD, Kinzler KW, Meltzer PS, George DL, and Vogelstein B, (1992) Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358: 80–83.

    Article  PubMed  CAS  Google Scholar 

  223. Onda M, Matsuda S, Higaki S, Iijima T, Fukushima J, Yokokura A, Kojima T, Horiuchi H, Kurokawa T, and Yamamoto T, (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77: 71–78.

    Article  PubMed  CAS  Google Scholar 

  224. Overholtzer M, Rao PH, Favis R, Lu XY, Elowitz MB, Barany F, Ladanyi M, Gorlick R, and Levine AJ, (2003) The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability. Proc Natl Acad Sci USA 100: 11547–11552.

    Article  PubMed  CAS  Google Scholar 

  225. Ozaki T, Neumann T, Wai D, Schafer KL, van Valen F, Lindner N, Scheel C, Bocker W, Winkelmann W, Dockhorn-Dworniczak B, Horst J, and Poremba C, (2003) Chromosomal alterations in osteosarcoma cell lines revealed by comparative genomic hybridization and multicolor karyotyping. Cancer Genet Cytogenet 140: 145–152.

    Article  PubMed  CAS  Google Scholar 

  226. Paget J, (1877) On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 60: 37–63.

    PubMed  CAS  Google Scholar 

  227. Papagelopoulos PJ, Galanis E, Sim FH, and Unni KK, (1999) Periosteal osteosarcoma. Orthopedics 22: 971–974.

    PubMed  CAS  Google Scholar 

  228. Park HR, Jung WW, Bacchini P, Bertoni F, Kim YW, and Park YK, (2006) Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract 202: 509–515.

    Article  PubMed  CAS  Google Scholar 

  229. Park HR, Jung WW, Bertoni F, Bacchini P, Park JH, Kim YW, and Park YK, (2004) Molecular analysis of p53, MDM2 and H-ras genes in low-grade central osteosarcoma. Pathol Res Pract 200: 439–445.

    Article  PubMed  CAS  Google Scholar 

  230. Parkin DM, Stiller CA, and Nectoux J, (1993) International variations in the incidence of childhood bone tumors. Int J Cancer 53: 371–376.

    Article  PubMed  CAS  Google Scholar 

  231. Pellin A, Boix-Ferrero J, Carpio D, Lopez-Terrada D, Carda C, Navarro S, Peydro-Olaya A, Triche TJ, and Llombart-Bosch A, (1997) Molecular alterations of the RB1, TP53, and MDM2 genes in primary and xenografted human osteosarcomas. Diagn Mol Pathol 6: 333–341.

    Article  PubMed  CAS  Google Scholar 

  232. Petkovic M, Dietschy T, Freire R, Jiao R, and Stagljar I, (2005) The human Rothmund–Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J Cell Sci 118: 4261–4269.

    Article  PubMed  CAS  Google Scholar 

  233. Pommier Y, Weinstein JN, Aladjem MI, and Kohn KW, (2006) Chk2 molecular interaction map and rationale for Chk2 inhibitors. Clin Cancer Res 12: 2657–2661.

    Article  PubMed  CAS  Google Scholar 

  234. Porter DE, Holden ST, Steel CM, Cohen BB, Wallace MR, and Reid R, (1992) A significant proportion of patients with osteosarcoma may belong to Li–Fraumeni cancer families. J Bone Joint Surg Br 74: 883–886.

    PubMed  CAS  Google Scholar 

  235. Price CH and Goldie W, (1969) Paget’s sarcoma of bone. A study of eighty cases from the Bristol and the Leeds bone tumour registries. J Bone Joint Surg Br 51: 205–224.

    Google Scholar 

  236. Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, Huvos AG, Betcher DL, Baum ES, Kisker CT, and Miser JS, (1997) Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol 15: 76–84.

    Google Scholar 

  237. Radig K, Schneider-Stock R, Oda Y, Neumann W, Mittler U, and Roessner A, (1996) Mutation spectrum of p53 gene in highly malignant human osteosarcomas. Gen Diagn Pathol 142: 25–32.

    PubMed  CAS  Google Scholar 

  238. Ragazzini P, Gamberi G, Benassi MS, Orlando C, Sestini R, Ferrari C, Molendini L, Sollazzo MR, Merli M, Magagnoli G, Bertoni F, Bohling T, Pazzagli M, and Picci P, (1999) Analysis of SAS gene and CDK4 and MDM2 proteins in low-grade osteosarcoma. Cancer Detect Prev 23: 129–136.

    Article  PubMed  CAS  Google Scholar 

  239. Rajagopalan H and Lengauer C, (2004) Aneuploidy and cancer. Nature 432: 338–341.

    Article  CAS  Google Scholar 

  240. Rajagopalan H, Nowak MA, Vogelstein B, and Lengauer C, (2003) The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer 3: 695–701.

    Article  PubMed  CAS  Google Scholar 

  241. Raymond AK, (1991) Surface osteosarcoma. Clin Orthop Relat Res 140–148.

    Google Scholar 

  242. Reddy SV, (2004) Etiology of Paget’s disease and osteoclast abnormalities. J Cell Biochem 93: 688–696.

    Article  PubMed  CAS  Google Scholar 

  243. Reith JD, Donahue FI, and Hornicek FJ, (1999) Dedifferentiated parosteal osteosarcoma with rhabdomyosarcomatous differentiation. Skeletal Radiol 28: 527-531.

    Article  PubMed  CAS  Google Scholar 

  244. Reya T, Morrison SJ, Clarke MF, and Weissman IL, (2001) Stem cells, cancer, and cancer stem cells. Nature 414: 105–111.

    Article  PubMed  CAS  Google Scholar 

  245. Ritts GD, Pritchard DJ, Unni KK, Beabout JW, and Eckardt JJ, (1987) Periosteal osteosarcoma. Clin Orthop Relat Res 299–307.

    Google Scholar 

  246. Rose PS, Dickey ID, Wenger DE, Unni KK, and Sim FH, (2006) Periosteal osteosarcoma: long-term outcome and risk of late recurrence. Clin Orthop Relat Res 453: 314–317.

    Article  PubMed  Google Scholar 

  247. Roskoski R, Jr., (2004) The ErbB/HER receptor protein-tyrosine kinases and cancer. Biochem Biophys Res Commun 319: 1–11.

    Article  PubMed  CAS  Google Scholar 

  248. Ross JS and Fletcher JA, (1998) The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 16: 413–428.

    Article  PubMed  CAS  Google Scholar 

  249. Rothmund A, (1868) Ueber Cataracte in Verbindung mit einer eigenthuemlichen Hautdegeneration. Albrecht von Graefes Arch Klin Exp Ophthal 14: 159–182.

    Article  Google Scholar 

  250. Ruther U, Komitowski D, Schubert FR, and Wagner EF, (1989) c-fos expression induces bone tumors in transgenic mice. Oncogene 4: 861–865.

    PubMed  CAS  Google Scholar 

  251. Salas S, Bartoli C, Deville JL, Gaudart J, Fina F, Calisti A, Bollini G, Curvale G, Gentet JC, Duffaud F, Figarella-Branger D, and Bouvier C, (2007) Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch 451: 999–1007.

    Article  PubMed  CAS  Google Scholar 

  252. Sangiorgi L, Gobbi GA, Lucarelli E, Sartorio SM, Mordenti M, Ghedini I, Maini V, Scrimieri F, Reggiani M, Bertoja AZ, Benassi MS, and Picci P, (2001) Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness. Int J Cancer 95: 156–161.

    Article  PubMed  CAS  Google Scholar 

  253. Sato K, Yamamura S, Iwata H, Sugiura H, Nakashima N, and Nagasaka T, (1996) Giant cell-rich osteosarcoma: a case report. Nagoya J Med Sci 59: 151–157.

    Google Scholar 

  254. Schajowicz F, McGuire MH, Santini Araujo E, Muscolo DL, and Gitelis S, (1988) Osteosarcomas arising on the surfaces of long bones. J Bone Joint Surg Am 70: 555–564.

    PubMed  CAS  Google Scholar 

  255. Scheel C, Schaefer KL, Jauch A, Keller M, Wai D, Brinkschmidt C, van Valen F, Boecker W, Dockhorn-Dworniczak B, and Poremba C, (2001) Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas. Oncogene 20: 3835–3844.

    Article  PubMed  CAS  Google Scholar 

  256. Scheffer H, Kruize YC, Osinga J, Kuiken G, Oosterhuis JW, Leeuw JA, Schraffordt Koops H, and Buys CH, (1991) Complete association of loss of heterozygosity of chromosomes 13 and 17 in osteosarcoma. Cancer Genet Cytogenet 53: 45–55.

    Article  PubMed  CAS  Google Scholar 

  257. Scholz RB, Kabisch H, Weber B, Roser K, Delling G, and Winkler K, (1992) Studies of the RB1 gene and the p53 gene in human osteosarcomas. Pediatr Hematol Oncol 9: 125–137.

    Article  PubMed  CAS  Google Scholar 

  258. Selvarajah S, Yoshimoto M, Maire G, Paderova J, Bayani J, Squire JA, and Zielenska M, (2007) Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. Cancer Genet Cytogenet 179: 52–61.

    Article  PubMed  CAS  Google Scholar 

  259. Selvarajah S, Yoshimoto M, Park PC, Maire G, Paderova J, Bayani J, Lim G, Al-Romaih K, Squire JA, and Zielenska M, (2006) The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma. Chromosoma 115: 459–467.

    Article  PubMed  CAS  Google Scholar 

  260. Serra M, Tarkkanen M, Baldini N, Scotlandi K, Sarti M, Maurici D, Manara MC, Benini S, Bacchini P, Knuutila S, and Picci P, (2001) Simultaneous paired analysis of numerical chromosomal aberrations and DNA content in osteosarcoma. Mod Pathol 14: 710–716.

    Article  PubMed  CAS  Google Scholar 

  261. Seton M, Choi HK, Hansen MF, Sebaldt RJ, and Cooper C, (2003) Analysis of environmental factors in familial versus sporadic Paget’s disease of bone – the New England Registry for Paget’s disease of bone. J Bone Miner Res 18: 1519–1524.

    Article  PubMed  Google Scholar 

  262. Sheth DS, Yasko AW, Raymond AK, Ayala AG, Carrasco CH, Benjamin RS, Jaffe N, and Murray JA, (1996) Conventional and dedifferentiated parosteal osteosarcoma. Diagnosis, treatment, and outcome. Cancer 78: 2136–2145.

    CAS  Google Scholar 

  263. Shih IM, Zhou W, Goodman SN, Lengauer C, Kinzler KW, and Vogelstein B, (2001) Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. Cancer Res 61: 818–822.

    PubMed  CAS  Google Scholar 

  264. Sieber OM, Heinimann K, and Tomlinson IP, (2003) Genomic instability – the engine of tumorigenesis? Nat Rev Cancer 3: 701–708.

    Article  PubMed  CAS  Google Scholar 

  265. Siris ES, (1998) Paget’s disease of bone. J Bone Miner Res 13: 1061–1065.

    Article  PubMed  CAS  Google Scholar 

  266. Siris ES, Jacobs TP, and Canfield RE, (1980) Paget’s disease of bone. Bull N Y Acad Med 56: 285–304.

    PubMed  CAS  Google Scholar 

  267. Siris ES, Ottman R, Flaster E, and Kelsey JL, (1991) Familial aggregation of Paget’s disease of bone. J Bone Miner Res 6: 495-500.

    Article  PubMed  CAS  Google Scholar 

  268. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, and McGuire WL, (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177–182.

    Article  PubMed  CAS  Google Scholar 

  269. Slootweg PJ and Muller H, (1985) Osteosarcoma of the jaw bones. Analysis of 18 cases. J Maxillofac Surg 13: 158–166.

    Article  Google Scholar 

  270. Smith J, Botet JF, and Yeh SD, (1984) Bone sarcomas in Paget’s Disease: a study of 85 patients. Radiology 152: 583–590.

    PubMed  CAS  Google Scholar 

  271. Somers GR, Ho M, Zielenska M, Squire JA, and Thorner PS, (2005) HER2 amplification and overexpression is not present in pediatric osteosarcoma: a tissue microarray study. Pediatr Dev Pathol 8: 525–532.

    Article  PubMed  CAS  Google Scholar 

  272. Sotillo-Pineiro E, Sierrasesumaga L, and Patino-Garcia A, (2004) Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients. Pediatr Res 55: 231–235.

    Article  PubMed  CAS  Google Scholar 

  273. Squire JA, Pei J, Marrano P, Beheshti B, Bayani J, Lim G, Moldovan L, and Zielenska M, (2003) High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer 38: 215–225.

    Article  PubMed  CAS  Google Scholar 

  274. Stemmer-Rachamimov AO, Nielsen GP, Rosenberg AE, Louis DN, Jones D, Ramesh V, Gusella JF, and Jacoby LB, (1998) The NF2 gene and merlin protein in human osteosarcomas. Neurogenetics 2: 73–74.

    Article  PubMed  CAS  Google Scholar 

  275. Stewart SA, (2005) Telomere maintenance and tumorigenesis: an “ALT”ernative road. Curr Mol Med 5: 253–257.

    Article  PubMed  CAS  Google Scholar 

  276. Stiewe T, (2007) The p53 family in differentiation and tumorigenesis. Nat Rev Cancer 7: 165–168.

    Article  PubMed  CAS  Google Scholar 

  277. Stock C, Kager L, Fink FM, Gadner H, and Ambros PF, (2000) Chromosomal regions involved in the pathogenesis of osteosarcomas. Genes Chromosomes Cancer 28: 329–336.

    Article  PubMed  CAS  Google Scholar 

  278. Sweeney C and Carraway KL, 3rd, (2000) Ligand discrimination by ErbB receptors: differential signaling through differential phosphorylation site usage. Oncogene 19: 5568–5573.

    Article  CAS  Google Scholar 

  279. Sweeney C, Fambrough D, Huard C, Diamonti AJ, Lander ES, Cantley LC, and Carraway KL, 3rd, (2001) Growth factor-specific signaling pathway stimulation and gene expression mediated by ErbB receptors. J Biol Chem 276: 22685–22698.

    Article  PubMed  CAS  Google Scholar 

  280. Takeuchi K, Morii T, Yabe H, Morioka H, Mukai M, and Toyama Y, (2006) Dedifferentiated parosteal osteosarcoma with well-differentiated metastases. Skeletal Radiol 35: 778–782.

    Article  PubMed  Google Scholar 

  281. Tamrakar S, Rubin E, and Ludlow JW, (2000) Role of pRB dephosphorylation in cell cycle regulation. Front Biosci 5: D121–137.

    Article  PubMed  CAS  Google Scholar 

  282. Tan X, Martin SJ, Green DR, and Wang JY, (1997) Degradation of retinoblastoma protein in tumor necrosis factor- and CD95-induced cell death. J Biol Chem 272: 9613–9616.

    Article  PubMed  CAS  Google Scholar 

  283. Tan X and Wang JY, (1998) The caspase-RB connection in cell death. Trends Cell Biol 8: 116–120.

    Article  Google Scholar 

  284. Tanzawa H, Uchiyama S, and Sato K, (1991) Statistical observation of osteosarcoma of the maxillofacial region in Japan. Analysis of 114 Japanese cases reported between 1930 and 1989. Oral Surg Oral Med Oral Pathol 72: 444–448.

    Article  PubMed  CAS  Google Scholar 

  285. Tarkkanen M, Bohling T, Gamberi G, Ragazzini P, Benassi MS, Kivioja A, Kallio P, Elomaa I, Picci P, and Knuutila S, (1998) Comparative genomic hybridization of low-grade central osteosarcoma. Mod Pathol 11: 421–426.

    PubMed  CAS  Google Scholar 

  286. Tarkkanen M, Elomaa I, Blomqvist C, Kivioja AH, Kellokumpu-Lehtinen P, Bohling T, Valle J, and Knuutila S, (1999) DNA sequence copy number increase at 8q: a potential new prognostic marker in high-grade osteosarcoma. Int J Cancer 84: 114–121.

    Article  PubMed  CAS  Google Scholar 

  287. Tarkkanen M, Karhu R, Kallioniemi A, Elomaa I, Kivioja AH, Nevalainen J, Bohling T, Karaharju E, Hyytinen E, Knuutila S, et al., (1995) Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res 55: 1334–1338.

    PubMed  CAS  Google Scholar 

  288. Taylor SL, Rudland PS, and Barraclough R, (1999) C-erbB-2 mRNA in breast cancer specimens that exhibit membrane or cytoplasmic immunoreactivity for c-erbB-2. Oncol Res 11: 311–317.

    PubMed  CAS  Google Scholar 

  289. Thomas DG, Giordano TJ, Sanders D, Biermann JS, and Baker L, (2002) Absence of HER2/neu gene expression in osteosarcoma and skeletal Ewing’s sarcoma. Clin Cancer Res 8: 788–793.

    PubMed  CAS  Google Scholar 

  290. Thomson MS, (1936) Poikiloderma congenitale. Brit J Derm 48: 221–234.

    Article  Google Scholar 

  291. Toguchida J, Yamaguchi T, Dayton SH, Beauchamp RL, Herrera GE, Ishizaki K, Yamamuro T, Meyers PA, Little JB, Sasaki MS, et al., (1992) Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. N Engl J Med 326: 1301–1308.

    Article  PubMed  CAS  Google Scholar 

  292. Toledo F and Wahl GM, (2006) Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer 6: 909–923.

    Article  CAS  Google Scholar 

  293. Tomlinson I and Bodmer W, (1999) Selection, the mutation rate and cancer: ensuring that the tail does not wag the dog. Nat Med 5: 11–12.

    Article  CAS  Google Scholar 

  294. Tsai JY, Aviv H, Benevenia J, Chang VT, Patterson F, Aisner S, and Hameed M, (2004) HER-2/neu and p53 in osteosarcoma: an immunohistochemical and fluorescence in situ hybridization analysis. Cancer Invest 22: 16–24.

    Article  PubMed  CAS  Google Scholar 

  295. Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, Ratzkin BJ, and Yarden Y, (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 16: 5276–5287.

    PubMed  CAS  Google Scholar 

  296. Ulaner GA, Huang HY, Otero J, Zhao Z, Ben-Porat L, Satagopan JM, Gorlick R, Meyers P, Healey JH, Huvos AG, Hoffman AR, and Ladanyi M, (2003) Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma. Cancer Res 63: 1759–1763.

    PubMed  CAS  Google Scholar 

  297. Unni KK, (1998) Osteosarcoma of bone. J Orthop Sci 3: 287–294.

    Article  PubMed  CAS  Google Scholar 

  298. Unni KK and Dahlin DC, (1979) Premalignant tumors and conditions of bone. Am J Surg Pathol 3: 47–60.

    Article  Google Scholar 

  299. Unni KK, Dahlin DC, Beabout JW, and Ivins JC, (1976) Parosteal osteogenic sarcoma. Cancer 37: 2466–2475.

    Article  PubMed  CAS  Google Scholar 

  300. Valabrega G, Fagioli F, Corso S, Madon E, Brach del Prever A, Biasin E, Linari A, Aglietta M, and Giordano S, (2003) ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells. Br J Cancer 88: 396–400.

    Article  PubMed  CAS  Google Scholar 

  301. van Brabant AJ, Stan R, and Ellis NA, (2000) DNA helicases, genomic instability, and human genetic disease. Annu Rev Genomics Hum Genet 1: 409–459.

    Article  PubMed  Google Scholar 

  302. van Gent DC, Hoeijmakers JH, and Kanaar R, (2001) Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet 2: 196–206.

    Article  PubMed  Google Scholar 

  303. van Straaten F, Muller R, Curran T, Van Beveren C, and Verma IM, (1983) Complete nucleotide sequence of a human c-onc gene: deduced amino acid sequence of the human c-fos protein. Proc Natl Acad Sci USA 80: 3183–3187.

    Article  PubMed  Google Scholar 

  304. Vener J, Rice DH, and Newman AN, (1984) Osteosarcoma and chondrosarcoma of the head and neck. Laryngoscope 94: 240–242.

    Article  PubMed  CAS  Google Scholar 

  305. Vennos EM and James WD, (1995) Rothmund–Thomson syndrome. Dermatol Clin 13: 143–150.

    Google Scholar 

  306. Vousden KH and Lu X, (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2: 594–604.

    Article  CAS  Google Scholar 

  307. Wadayama B, Toguchida J, Shimizu T, Ishizaki K, Sasaki MS, Kotoura Y, and Yamamuro T, (1994) Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res 54: 3042–3048.

    PubMed  CAS  Google Scholar 

  308. Wadayama B, Toguchida J, Yamaguchi T, Sasaki MS, and Yamamuro T, (1993) p53 expression and its relationship to DNA alterations in bone and soft tissue sarcomas. Br J Cancer 68: 1134–1139.

    Article  PubMed  CAS  Google Scholar 

  309. Wajant H, (2002) The Fas signaling pathway: more than a paradigm. Science 296: 1635–1636.

    Article  PubMed  CAS  Google Scholar 

  310. Wang JY, Naderi S, and Chen TT, (2001) Role of retinoblastoma tumor suppressor protein in DNA damage response. Acta Oncol 40: 689–695.

    Article  PubMed  CAS  Google Scholar 

  311. Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, and Plon SE, (2003) Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund–Thomson syndrome. J Natl Cancer Inst 95: 669–674.

    Article  PubMed  CAS  Google Scholar 

  312. Wang X, (2001) The expanding role of mitochondria in apoptosis. Genes Dev 15: 2922–2933.

    PubMed  CAS  Google Scholar 

  313. Wang ZQ, Liang J, Schellander K, Wagner EF, and Grigoriadis AE, (1995) c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. Cancer Res 55: 6244–6251.

    PubMed  CAS  Google Scholar 

  314. Wang ZQ, Ovitt C, Grigoriadis AE, Mohle-Steinlein U, Ruther U, and Wagner EF, (1992) Bone and haematopoietic defects in mice lacking c-fos. Nature 360: 741–745.

    Article  PubMed  CAS  Google Scholar 

  315. Wei G, Lonardo F, Ueda T, Kim T, Huvos AG, Healey JH, and Ladanyi M, (1999) CDK4 gene amplification in osteosarcoma: reciprocal relationship with INK4A gene alterations and mapping of 12q13 amplicons. Int J Cancer 80: 199–204.

    Article  PubMed  CAS  Google Scholar 

  316. Weichselbaum RR, Beckett M, and Diamond A, (1988) Some retinoblastomas, osteosarcomas, and soft tissue sarcomas may share a common etiology. Proc Natl Acad Sci USA 85: 2106–2109.

    Article  PubMed  CAS  Google Scholar 

  317. Weiss A, Khoury JD, Hoffer FA, Wu J, Billups CA, Heck RK, Quintana J, Poe D, Rao BN, and Daw NC, (2007) Telangiectatic osteosarcoma: the St. Jude Children’s Research Hospital’s experience. Cancer 109: 1627–1637.

    Google Scholar 

  318. Werner SR, Prahalad AK, Yang J, and Hock JM, (2006) RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund–Thomson syndrome. Biochem Biophys Res Commun 345: 403–409.

    Article  PubMed  CAS  Google Scholar 

  319. Wick MR, Siegal GP, Unni KK, McLeod RA, and Greditzer HG, 3rd, (1981) Sarcomas of bone complicating osteitis deformans (Paget’s disease): fifty years’ experience. Am J Surg Pathol 5: 47–59.

    Article  PubMed  CAS  Google Scholar 

  320. Willmore-Payne C, Holden JA, Zhou H, Gupta D, Hirschowitz S, Wittwer CT, and Layfield LJ, (2006) Evaluation of Her-2/neu gene status in osteosarcoma by fluorescence in situ hybridization and multiplex and monoplex polymerase chain reactions. Arch Pathol Lab Med 130: 691–698.

    PubMed  CAS  Google Scholar 

  321. Wittig JC, Bickels J, Priebat D, Jelinek J, Kellar-Graney K, Shmookler B, and Malawer MM, (2002) Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. Am Fam Physician 65: 1123–1132.

    PubMed  Google Scholar 

  322. Wold LE, Unni KK, Beabout JW, Sim FH, and Dahlin DC, (1984) Dedifferentiated parosteal osteosarcoma. J Bone Joint Surg Am 66: 53–59.

    PubMed  CAS  Google Scholar 

  323. Wolf M, El-Rifai W, Tarkkanen M, Kononen J, Serra M, Eriksen EF, Elomaa I, Kallioniemi A, Kallioniemi OP, and Knuutila S, (2000) Novel findings in gene expression detected in human osteosarcoma by cDNA microarray. Cancer Genet Cytogenet 123: 128–132.

    Article  PubMed  CAS  Google Scholar 

  324. Wong KK, Tsang YT, Shen J, Cheng RS, Chang YM, Man TK, and Lau CC, (2004) Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA. Nucleic Acids Res 32: e69.

    Article  PubMed  CAS  Google Scholar 

  325. Woo LL, Futami K, Shimamoto A, Furuichi Y, and Frank KM, (2006) The Rothmund–Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress. Exp Cell Res 312: 3443–3457.

    Article  PubMed  CAS  Google Scholar 

  326. Worth LL, Lafleur EA, Jia SF, and Kleinerman ES, (2002) Fas expression inversely correlates with metastatic potential in osteosarcoma cells. Oncol Rep 9: 823–827.

    PubMed  CAS  Google Scholar 

  327. Wunder JS, Czitrom AA, Kandel R, and Andrulis IL, (1991) Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas. J Natl Cancer Inst 83: 194–200.

    Article  PubMed  CAS  Google Scholar 

  328. Wunder JS, Eppert K, Burrow SR, Gokgoz N, Bell RS, and Andrulis IL, (1999) Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas. Oncogene 18: 783–788.

    Article  PubMed  CAS  Google Scholar 

  329. Yamaguchi T, Toguchida J, Yamamuro T, Kotoura Y, Takada N, Kawaguchi N, Kaneko Y, Nakamura Y, Sasaki MS, and Ishizaki K, (1992) Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q. Cancer Res 52: 2419–2423.

    PubMed  CAS  Google Scholar 

  330. Yarden Y and Schlessinger J, (1987) Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 26: 1443–1451.

    Article  Google Scholar 

  331. Yarden Y and Schlessinger J, (1987) Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation. Biochemistry 26: 1434–1442.

    Article  Google Scholar 

  332. Yeh IT, (2002) Measuring HER-2 in breast cancer. Immunohistochemistry, FISH, or ELISA? Am J Clin Pathol 117 Suppl: S26–35.

    PubMed  Google Scholar 

  333. Zhang Y and Xiong Y, (2001) Control of p53 ubiquitination and nuclear export by MDM2 and ARF. Cell Growth Differ 12: 175–186.

    Google Scholar 

  334. Zhou H, Randall RL, Brothman AR, Maxwell T, Coffin CM, and Goldsby RE, (2003) Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 25: 27–32.

    Article  PubMed  Google Scholar 

  335. Zielenska M, Bayani J, Pandita A, Toledo S, Marrano P, Andrade J, Petrilli A, Thorner P, Sorensen P, and Squire JA, (2001) Comparative genomic hybridization analysis identifies gains of 1p35 approximately p36 and chromosome 19 in osteosarcoma. Cancer Genet Cytogenet 130: 14–21.

    Article  PubMed  CAS  Google Scholar 

  336. Zielenska M, Marrano P, Thorner P, Pei J, Beheshti B, Ho M, Bayani J, Liu Y, Sun BC, Squire JA, and Hao XS, (2004) High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue. Cytogenet Genome Res 107: 77–82.

    Article  PubMed  CAS  Google Scholar 

  337. Zou H, Henzel WJ, Liu X, Lutschg A, and Wang X, (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405–413.

    Article  PubMed  CAS  Google Scholar 

  338. Zucchini C, Bianchini M, Valvassori L, Perdichizzi S, Benini S, Manara MC, Solmi R, Strippoli P, Picci P, Carinci P, and Scotlandi K, (2004) Identification of candidate genes involved in the reversal of malignant phenotype of osteosarcoma cells transfected with the liver/bone/kidney alkaline phosphatase gene. Bone 34: 672–679.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT, USA

    Marc F. Hansen

Authors
  1. Marc F. Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag London

About this chapter

Cite this chapter

Hansen, M.F. (2010). Genetics of Osteosarcoma. In: Bone and Cancer. Topics in Bone Biology, vol 5. Springer, London. https://doi.org/10.1007/978-1-84882-019-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-84882-019-7_2

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84882-018-0

  • Online ISBN: 978-1-84882-019-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation