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Oncogenesis

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Musculoskeletal Research and Basic Science

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Abstract

Oncogenesis or cancer formation is the expression of impaired cellular events in the favor of uncontrolled cell growth and proliferation. This occurs basically by disruptions in harmonious control effects of the growth-inducing, growth-inhibiting, apoptosis-regulating, and DNA-repairing mechanisms. A simplified understanding of these mechanisms is given in this chapter. In the first part of the chapter, regarding the concepts of susceptibility to and formation of cancers, the basic knowledge of cellular genetic content and events is reviewed.In the second part, molecular basis of oncogenesis is explained regarding the eight hallmarks of cancers. For better understanding, well-described examples of mechanisms responsible in musculoskeletal system tumors are given through the text. Certainly, cellular and molecular aspects of oncogenesis will continue to be the primary field of future investigations to reach better understanding, diagnosis, treatment, and prediction of prognosis of cancers.

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References

  1. Yuan J, Fuchs B, Scully SP (2007) Molecular basis of cancer. In: OBS-3, Einhorn TA, O’Keefe RJ, Buckwalter JA (eds) Orthopaedic basic science, 3rd edn. American Academy of Orthopaedic Surgeons, Rosemont. ISBN: 139780892039340, Chapter 21, pp 379–393

    Google Scholar 

  2. Mitchell RN (2015) The cell as a unit of health and disease. In: Kumar V, Abbas AK, Aster JC (eds) Robbins and Cotran pathologic basis of disease, 9th edn. International edition, Philadelphia. ISBN: 978-0-8089-2450-0, Chapter 1, pp 1–29. 2015, by Saunders, an imprint of Elsevier Inc

    Google Scholar 

  3. Jones KB MD (2011) Musculoskeletal oncology. In: Flynn JM MD (ed) Orthopaedic knowledge update, 10th edn. American Academy of Orthopaedic Surgeons, Rosemont, pp 193–212, Chapter 17

    Google Scholar 

  4. Hall PA, Watt FM (1989) Stem cells: the generation and maintenance of cellular diversity. Development 106(4):619–633, Review

    CAS  PubMed  Google Scholar 

  5. Kafchinski LA, Jones KB (2014) MicroRNAs in osteosarcomagenesis. Adv Exp Med Biol 804:119–127. doi:10.1007/978-3-319-04843-7_6, Review

    Article  CAS  PubMed  Google Scholar 

  6. Miao J, Wu S, Peng Z, Tania M, Zhang C (2013) MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects. Tumour Biol 34(4):2093–2098, Review

    Article  CAS  PubMed  Google Scholar 

  7. Amary MF, Damato S, Halai D, Eskandarpour M, Berisha F, Bonar F, McCarthy S, Fantin VR, Straley KS, Lobo S, Aston W, Green CL, Gale RE, Tirabosco R, Futreal A, Campbell P, Presneau N, Flanagan AM (2011) Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. Nat Genet 43(12):1262–1265. doi:10.1038/ng.994

    Article  CAS  PubMed  Google Scholar 

  8. Lawlor ER, Thiele CJ (2012) Epigenetic changes in pediatric solid tumors: promising new targets. Clin Cancer Res 18(10):2768–2779. doi:10.1158/1078-0432.CCR-11-1921, Review

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Lee JY, Lee TH (2012) Effects of histone acetylation and CpG methylation on the structure of nucleosomes. Biochim Biophys Acta 1824(8):974–982. doi:10.1016/j.bbapap.2012.05.006, Epub 2012 May 22. Review

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M, Kroemer G (2010) Mitochondrial gateways to cancer. Mol Aspects Med 31(1):1–20. doi:10.1016/j.mam.2009.08.002, Epub 2009 Aug 19. Review

    Article  CAS  PubMed  Google Scholar 

  11. Gogvadze V, Zhivotovsky B, Orrenius S (2010) The Warburg effect and mitochondrial stability in cancer cells. Mol Aspects Med 31(1):60–74. doi:10.1016/j.mam.2009.12.004, Epub 2009 Dec 6. Review

    Article  CAS  PubMed  Google Scholar 

  12. Franceschi C (1989) Cell proliferation, cell death and aging. Aging (Milano) 1(1):3–15, Review

    CAS  Google Scholar 

  13. Tzen CY, Estervig DN, Minoo P, Filipak M, Maercklein PB, Hoerl BJ, Scott RE (1988) Differentiation, cancer, and anticancer activity. Biochem Cell Biol 66(6):478–489, Review

    Article  CAS  PubMed  Google Scholar 

  14. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70, Review

    Article  CAS  PubMed  Google Scholar 

  15. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013, Review

    Article  CAS  PubMed  Google Scholar 

  16. Kumar V, Abbas AK, Aster C (2015) Neoplasia. In: Kumar V, Abbas AK, Aster JC (eds) Robbins and Cotran pathologic basis of disease, 9th edn. International edition, Philadelphia, pp 265–340. ISBN: 978-0-8089-2450-0, Chapter 7. 2015, by Saunders, an imprint of Elsevier Inc

    Google Scholar 

  17. Krishnan B MS, Khanna G MD, Clohisy D MD (2008) Gene translocations in musculoskeletal neoplasms. Clin Orthop Relat Res 466(9):2131–2146

    Article  PubMed Central  PubMed  Google Scholar 

  18. Flanagan AM, Delaney D, O’Donnell P (2010) The benefits of molecular pathology in the diagnosis of musculoskeletal disease : part I of a two-part review: soft tissue tumors. Skeletal Radiol 39(2):105–115. doi:10.1007/s00256-009-0759-x

    Article  PubMed  Google Scholar 

  19. Flanagan AM, Delaney D, O’Donnell P (2010) Benefits of molecular pathology in the diagnosis of musculoskeletal disease : part II of a two-part review: bone tumors and metabolic disorders. Skeletal Radiol 39(3):213–224. doi:10.1007/s00256-009-0758-y

    Article  PubMed  Google Scholar 

  20. Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9(4):422–441, Review. (osteosarcoma oncogenes)

    Article  PubMed  Google Scholar 

  21. Perry JA, Kiezun A, Tonzi P, Van Allen EM, Carter SL, Baca SC, Cowley GS, Bhatt AS, Rheinbay E, Pedamallu CS, Helman E, Taylor-Weiner A, McKenna A, DeLuca DS, Lawrence MS, Ambrogio L, Sougnez C, Sivachenko A, Walensky LD, Wagle N, Mora J, de Torres C, Lavarino C, Dos Santos AS, Yunes JA, Brandalise SR, Mercado-Celis GE, Melendez-Zajgla J, Cárdenas-Cardós R, Velasco-Hidalgo L, Roberts CW, Garraway LA, Rodriguez-Galindo C, Gabriel SB, Lander ES, Golub TR, Orkin SH, Getz G, Janeway KA (2014) Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A 111(51):E5564–E5573. doi:10.1073/pnas.1419260111, Epub 2014 Dec PubMed PMID: 25512523, PubMed Central PMCID: PMC4280630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Puls F, Niblett AJ, Mangham DC (2014) Molecular pathology of bone tumours: diagnostic implications. Histopathology 64(4):461–476. doi:10.1111/his.12275

    Article  PubMed  Google Scholar 

  23. Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT (1994) A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor. ERG Nat Genet 6(2):146–151

    Article  CAS  PubMed  Google Scholar 

  24. Couvineau A, Wouters V, Bertrand G, Rouyer C, Gérard B, Boon LM, Grandchamp B, Vikkula M, Silve C (2008) PTHR1 mutations associated with Ollier disease result in receptor loss of function. Hum Mol Genet 17(18):2766–2775. doi:10.1093/hmg/ddn176

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Trosko JE, Chang CC, Upham BL, Tai MH (2004) Ignored hallmarks of carcinogenesis: stem cells and cell-cell communication. Ann N Y Acad Sci 1028:192–201, Review

    Article  CAS  PubMed  Google Scholar 

  26. Wang LL, Gannavarapu A, Kozinetz CA et al (2003) Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 95(9):669–674. doi:10.1093/jnci/95.9.669

    Article  CAS  PubMed  Google Scholar 

  27. Horvai A (2015) Bones, joints, and soft tissue tumors. In: Kumar V, Abbas AK, Aster JC (eds) Robbins and Cotran pathologic basis of disease, 9th edn. International edition, Philadelphia. ISBN: 978-0-8089-2450-0. Chapter 26, pp 1179–1226. 2015, by Saunders, an imprint of Elsevier Inc

    Google Scholar 

  28. Morcuende JA, Buckwalter JA (1997) New advances in the molecular biology of musculoskeletal neoplasms. Iowa Orthop J 17:115–120

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Sandberg AA, Bridge JA (2003) Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet 145(1):1–30, Review. (oncogenes)

    Article  CAS  PubMed  Google Scholar 

  30. Duhamel LA, Ye H, Halai D, Idowu BD, Presneau N, Tirabosco R, Flanagan AM (2012) Frequency of mouse double minute 2 (MDM2) and mouse double minute 4 (MDM4) amplification in parosteal and conventional osteosarcoma subtypes. Histopathology 60(2):357–359. doi:10.1111/j.1365-2559.2011.04023.x

    Article  PubMed  Google Scholar 

  31. Momand J, Jung D, Wilczynski S, Niland J (1998) The MDM2 gene amplification database. Nucleic Acids Res 26(15):3453–3459, Review

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Chufan EE, Sim HM, Ambudkar SV (2015) Molecular basis of the polyspecificity of P-glycoprotein (ABCB1): recent biochemical and structural studies. Adv Cancer Res 125:71–96. doi:10.1016/bs.acr.2014.10.003 (MDR-1)

    Article  PubMed  Google Scholar 

  33. Hattinger CM, Stoico G, Michelacci F, Pasello M, Scionti I, Remondini D, Castellani GC, Fanelli M, Scotlandi K, Picci P, Serra M (2009) Mechanisms of gene amplification and evidence of coamplification in drug-resistant human osteosarcoma cell lines. Genes Chromosomes Cancer 48(4):289–309. doi:10.1002/gcc.20640

    Article  CAS  PubMed  Google Scholar 

  34. Brownhill SC, Taylor C, Burchill SA (2007) Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT. Br J Cancer 96(12):1914–1923, Epub 2007 May 29

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Mohseny AB, Tieken C, van der Velden PA, Szuhai K, de Andrea C, Hogendoorn PC, Cleton-Jansen AM (2010) Small deletions but not methylations underlie CDKN2A/p16 loss of expression in conventional osteosarcoma. Genes Chromosomes Cancer 49(12):1095–1103. doi:10.1002/gcc.20817

    Article  CAS  PubMed  Google Scholar 

  36. Flynn RL, Cox KE, Jeitany M, Wakimoto H, Bryll AR, Ganem NJ, Bersani F, Pineda JR, Suvà ML, Benes CH, Haber DA, Boussin FD, Zou L (2015) Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 347(6219):273–277. doi:10.1126/science.1257216

    Article  CAS  PubMed  Google Scholar 

  37. Gocha AR, Nuovo G, Iwenofu OH, Groden J (2013) Human sarcomas are mosaic for telomerase-dependent and telomerase-independent telomere maintenance mechanisms: implications for telomere-based therapies. Am J Pathol 182(1):41–48. doi:10.1016/j.ajpath.2012.10.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Weng NP (2012) Telomeres and immune competency. Curr Opin Immunol 24(4):470–475. doi:10.1016/j.coi.2012.05.001, Epub 2012 May 22. Review

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Franovic A, Holterman CE, Payette J, Lee S (2009) Human cancers converge at the HIF-2alpha oncogenic axis. Proc Natl Acad Sci U S A 106(50):21306–21311. doi:10.1073/pnas.0906432106, Epub 2009 Dec 2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Marxsen JH, Stengel P, Doege K, Heikkinen P, Jokilehto T, Wagner T, Jelkmann W, Jaakkola P, Metzen E (2004) Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-alpha-prolyl-4-hydroxylases. Biochem J 381(Pt 3):761–767

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Klotzsche-von Ameln A, Prade I, Grosser M, Kettelhake A, Rezaei M, Chavakis T, Flamme I, Wielockx B, Breier G (2013) PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-α. Mol Cancer Res 11(11):1337–1348. doi:10.1158/1541-7786.MCR-13-0201, Epub 2013 Sep 18

    Article  CAS  PubMed  Google Scholar 

  42. Kashima T, Kawaguchi J, Takeshita S, Kuroda M, Takanashi M, Horiuchi H, Imamura T, Ishikawa Y, Ishida T, Mori S, Machinami R, Kudo A (1999) Anomalous cadherin expression in osteosarcoma. Possible relationships to metastasis and morphogenesis. Am J Pathol 155(5):1549–1555

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Kingsley LA, Fournier PG, Chirgwin JM, Guise TA (2007) Molecular biology of bone metastasis. Mol Cancer Ther 6(10):2609–2617

    Article  CAS  PubMed  Google Scholar 

  44. Matuschek C, Lehnhardt M, Gerber PA, Poremba C, Hamilton J, Lammering G, Orth K, Budach W, Bojar H, Bölke E, Peiper M (2014) Increased CD44s and decreased CD44v6 RNA expression are associated with better survival in myxofibrosarcoma patients: a pilot study. Eur J Med Res 19:6. doi:10.1186/2047-783X-19-6

    Article  PubMed Central  PubMed  Google Scholar 

  45. Sancéau J, Truchet S, Bauvois B (2003) Matrix metalloproteinase-9 silencing by RNA interference triggers the migratory-adhesive switch in Ewing’s sarcoma cells. J Biol Chem 278(38):36537–36546, Epub 2003 Jul 7

    Article  PubMed  Google Scholar 

  46. Ramaswamy S, Ross KN, Lander ES, Golub TR (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33(1):49–54, Epub 2002

    Article  CAS  PubMed  Google Scholar 

  47. Cavallo F, De Giovanni C, Nanni P, Forni G, Lollini PL (2011) The immune hallmarks of cancer. Cancer Immunol Immunother 60(3):319–326. doi:10.1007/s00262-010-0968-0

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7):1073–1081. doi:10.1093/carcin/bgp127, Epub 2009 May 25. Review

    Article  CAS  PubMed  Google Scholar 

  49. Holzer G, Pfandlsteiner T, Blahovec H, Trieb K, Kotz R (2003) Serum levels of TNF-beta and sTNF-R in patients with malignant bone tumours. Anticancer Res 23(3C):3057–3059

    CAS  PubMed  Google Scholar 

  50. Oliveira ID, Petrilli AS, Tavela MH, Zago MA, de Toledo SR (2007) TNF-alpha, TNF-beta, IL-6, IL-10, PECAM-1 and the MPO inflammatory gene polymorphisms in osteosarcoma. J Pediatr Hematol Oncol 29(5):293–297

    Article  CAS  PubMed  Google Scholar 

  51. Susnow N, Zeng L, Margineantu D, Hockenbery DM (2009) Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 19(1):42–49. doi:10.1016/j.semcancer.2008.12.002, Epub 2008 Dec 24. Review

    Article  CAS  PubMed  Google Scholar 

  52. Tennant DA, Durán RV, Boulahbel H, Gottlieb E (2009) Metabolic transformation in cancer. Carcinogenesis 30(8):1269–1280. doi:10.1093/carcin/bgp070, Epub 2009 Mar 25. Review

    Article  CAS  PubMed  Google Scholar 

  53. Trieb K, Lechleitner T, Lang S, Windhager R, Kotz R, Dirnhofer S (1998) Evaluation of HLA-DR expression and T-lymphocyte infiltration in osteosarcoma. Pathol Res Pract 194(10):679–684

    Article  CAS  PubMed  Google Scholar 

  54. Bonuccelli G, Avnet S, Grisendi G, Salerno M, Granchi D, Dominici M, Kusuzaki K, Baldini N (2014) Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells. Oncotarget 5(17):7575–7588

    Article  PubMed Central  PubMed  Google Scholar 

  55. Dang CV, Hamaker M, Sun P, Le A, Gao P (2011) Therapeutic targeting of cancer cell metabolism. J Mol Med (Berl) 89(3):205–212. doi:10.1007/s00109-011-0730-x, Epub 2011 Feb 8. Review

    Article  CAS  Google Scholar 

  56. Giang AH, Raymond T, Brookes P, de Mesy Bentley K, Schwarz E, O’Keefe R, Eliseev R (2013) Mitochondrial dysfunction and permeability transition in osteosarcoma cells showing the Warburg effect. J Biol Chem 288(46):33303–33311. doi:10.1074/jbc.M113.507129, Epub 2013 Oct 7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11(8):618. doi:10.1038/nrc3038, Epub 2011 Apr 14. Review. Erratum in

    Article  CAS  Google Scholar 

  58. Ortega AD, Sánchez-Aragó M, Giner-Sánchez D, Sánchez-Cenizo L, Willers I, Cuezva JM (2009) Glucose avidity of carcinomas. Cancer Lett 276(2):125–135. doi:10.1016/j.canlet.2008.08.007, Epub 2008 Sep 14. Review

    Article  CAS  PubMed  Google Scholar 

  59. Sotgia F, Martinez-Outschoorn UE, Lisanti MP (2014) The reverse Warburg effect in osteosarcoma. Oncotarget 5(18):7982–7983

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, School of Medicine, University of Mersin, Mersin, Turkey

    Metin Manouchehr Eskandari MD

  2. Department of Orthopaedics and Traumatology, School of Medicine, İstanbul Medeniyet University, İstanbul, Turkey

    İrfan Esenkaya MD

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  1. Metin Manouchehr Eskandari MD
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Correspondence to Metin Manouchehr Eskandari MD .

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  1. Department of Sports Medicine, Hacettepe University Medical Faculty, Ankara, Turkey

    Feza Korkusuz

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Eskandari, M.M., Esenkaya, İ. (2016). Oncogenesis. In: Korkusuz, F. (eds) Musculoskeletal Research and Basic Science. Springer, Cham. https://doi.org/10.1007/978-3-319-20777-3_34

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  • DOI: https://doi.org/10.1007/978-3-319-20777-3_34

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