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Molecular biology and cytogenetics of soft tissue sarcomas: Relevance for targeted therapies

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Targeting Treatment of Soft Tissue Sarcomas

Part of the book series: Cancer Treatment and Research ((CTAR,volume 120))

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References

  1. Greco, A., Roccato, E., Miranda, C., Cleris, L., Formelli, F., and Pierotti, M. A. Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int. J. Cancer, 92: 354–360, 2001.

    Article  CAS  PubMed  Google Scholar 

  2. O’Brien, K. P., Seroussi, E., Dal Cin, P., Sciot, R., Mandahl, N., Fletcher, J. A., Turc-Carel, C., and Dumanski, J. P. Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas. Genes Chromosomes. Cancer, 23: 187–193, 1998.

    Google Scholar 

  3. Hirota, S., Isozaki, K., Moriyama, Y., Hashimoto, K., Nishida, T., Ishiguro, S., Kawano, K., Hanada, M., Kurata, A., Takeda, M., Muhammad Tunio, G., Matsuzawa, Y., Kanakura, Y., Shinomura, Y., and Kitamura, Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science, 279: 577–580, 1998.

    Article  CAS  PubMed  Google Scholar 

  4. Sandberg, A. A., Turc-Carel, C., and Gemmill, R. M. Chromosomes in solid tumors and beyond. Cancer Res., 48: 1049–1059, 1988.

    CAS  PubMed  Google Scholar 

  5. Fletcher, J. A., Kozakewich, H. P., Hoffer, F. A., Lage, J. M., Weidner, N., Tepper, R., Pinkus, G. S., Morton, C. C., and Corson, J. M. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N. Engl. J. Med., 324: 436–442, 1991.

    CAS  PubMed  Google Scholar 

  6. Sandberg, A. A. and Bridge, J. A. The Cytogenetics of Bone and Soft Tissue Tumors. Austin: R.G. Landes Company, 1995.

    Google Scholar 

  7. Heim, S. and Mitelman, F. Cancer Cytogenetics, Second ed. New York: Wiley-Liss, 1995.

    Google Scholar 

  8. Sreekantaiah, C., Ladanyi, M., Rodriguez, E., and Chaganti, R. S. Chromosomal aberrations in soft tissue tumors. Relevance to diagnosis, classification, and molecular mechanisms. Am. J. Pathol., 144: 1121–1134, 1994.

    CAS  PubMed  Google Scholar 

  9. Tontonoz, P., Singer, S., Forman, B. M., Sarraf, P., Fletcher, J. A., Fletcher, C. D., Brun, R. P., Mueller, E., Altiok, S., Oppenheim, H., Evans, R. M., and Spiegelman, B. M. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc. Natl. Acad. Sci. U. S. A., 94: 237–241, 1997.

    Article  CAS  PubMed  Google Scholar 

  10. Demetri, G. D., Fletcher, C. D., Mueller, E., Sarraf, P., Naujoks, R., Campbell, N., Spiegelman, B. M., and Singer, S. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. U. S. A, 96: 3951–3956, 1999.

    Article  CAS  PubMed  Google Scholar 

  11. Turc-Carel, C., Limon, J., Dal Cin, P., Rao, U., Karakousis, C., and Sandberg, A. A. Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas. Cancer Genet. Cytogenet., 23: 291–299, 1986.

    CAS  PubMed  Google Scholar 

  12. Sreekantaiah, C., Karakousis, C. P., Leong, S. P., and Sandberg, A. A. Cytogenetic findings in liposarcoma correlate with histopathologic subtypes. Cancer, 69: 2484–2495, 1992.

    CAS  PubMed  Google Scholar 

  13. Fletcher, C. D., Akerman, M., Dal Cin, P., De Wever, I., Mandahl, N., Mertens, F., Mitelman, F., Rosai, J., Rydholm, A., Sciot, R., Tallini, G., Van Den Berghe, H., Van de Ven, W., Vanni, R., and Willen, H. Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am. J. Pathol., 148: 623–630, 1996.

    CAS  PubMed  Google Scholar 

  14. Hisaoka, M., Tsuji, S., Morimitsu, Y., Hashimoto, H., Shimajiri, S., Komiya, S., and Ushijima, M. Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Diagn. Mol. Pathol., 7: 96–101, 1998.

    Article  CAS  PubMed  Google Scholar 

  15. Kuroda, M., Ishida, T., Horiuchi, H., Kida, N., Uozaki, H., Takeuchi, H., Tsuji, K., Imamura, T., Mori, S., and Machinami, R. Chimeric TLS/FUS-CHOP gene expression and the heterogeneity of its junction in human myxoid and round cell liposarcoma. Am. J. Pathol., 147: 1221–1227, 1995.

    CAS  PubMed  Google Scholar 

  16. Aman, P., Ron, D., Mandahl, N., Fioretos, T., Heim, S., Arheden, K., Willen, H., Rydholm, A., and Mitelman, F. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chromosom. Cancer, 5: 278–285, 1992.

    CAS  PubMed  Google Scholar 

  17. Crozat, A., Aman, P., Mandahl, N., and Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature, 363: 640–644, 1993.

    Article  CAS  PubMed  Google Scholar 

  18. Mandahl, N., Heim, S., Arheden, K., Rydholm, A., Willen, H., and Mitelman, F. Rings, dicentrics, and telomeric association in histiocytomas. Cancer Genet. Cytogenet., 30: 23–33, 1988.

    CAS  PubMed  Google Scholar 

  19. Turc-Carel, C., Dal Cin, P., Rao, U., Karakousis, C., and Sandberg, A. A. Recurrent breakpoints at 9q31 and 22q12.2 in extraskeletal myxoid chondrosarcoma. Cancer Genet. Cytogenet., 30: 145–150, 1988.

    Article  CAS  PubMed  Google Scholar 

  20. Pedeutour, F., Forus, A., Coindre, J. M., Berner, J. M., Nicolo, G., Michiels, J. F., Terrier, P., Ranchere-Vince, D., Collin, F., Myklebost, O., and Turc-Carel, C. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes. Cancer, 24: 30–41, 1999.

    Article  CAS  PubMed  Google Scholar 

  21. Zucman, J., Delattre, O., Desmaze, C., Epstein, A. L., Stenman, G., Speleman, F., Fletchers, C. D., Aurias, A., and Thomas, G. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat. Genet., 4: 341–345, 1993.

    Article  CAS  PubMed  Google Scholar 

  22. Brown, A. D., Lopez-Terrada, D., Denny, C., and Lee, K. A. Promoters containing ATF-binding sites are de-regulated in cells that express the EWS/ATF1 oncogene. Oncogene, 10: 1749–1756, 1995.

    CAS  PubMed  Google Scholar 

  23. Gerald, W. L., Miller, H. K., Battifora, H., Miettinen, M., Silva, E. G., and Rosai, J. Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. Am. J. Surg. Pathol., 15: 499–513, 1991.

    CAS  PubMed  Google Scholar 

  24. Ladanyi, M. and Gerald, W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res., 54: 2837–2840, 1994.

    CAS  PubMed  Google Scholar 

  25. Gerald, W. L., Ladanyi, M., de Alava, E., Cuatrecasas, M., Kushner, B. H., LaQuaglia, M. P., and Rosai, J. Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J. Clin. Oncol., 16: 3028–3036, 1998.

    CAS  PubMed  Google Scholar 

  26. Rodriguez, E., Sreekantaiah, C., Gerald, W., Reuter, V. E., Motzer, R. J., and Chaganti, R. S. A recurring translocation, t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell tumors. Cancer Genet. Cytogenet., 69: 17–21, 1993.

    Article  CAS  PubMed  Google Scholar 

  27. Biegel, J. A., Conard, K., and Brooks, J. J. Translocation (11;22)(p13;q12): primary change in intra-abdominal desmoplastic small round cell tumor. Genes Chromosom. Cancer, 7: 119–121, 1993.

    CAS  PubMed  Google Scholar 

  28. Lee, S. B., Kolquist, K. A., Nichols, K., Englert, C., Maheswaran, S., Ladanyi, M., Gerald, W. L., and Haber, D. A. The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. Nat. Genet., 17: 309–313, 1997.

    CAS  PubMed  Google Scholar 

  29. Kelly, J. D., Haldeman, B. A., Grant, F. J., Murray, M. J., Seifert, R. A., Bowen-Pope, D. F., Cooper, J. A., and Kazlauskas, A. Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation. J. Biol. Chem., 266: 8987–8992, 1991.

    CAS  PubMed  Google Scholar 

  30. Delattre, O., Zucman, J., Plougastel, B., Desmaze, C., Melot, T., Peter, M., Kovar, H., Joubert, I., de Jong, P., Rouleau, G., and et al Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature, 359: 162–165, 1992.

    Article  CAS  PubMed  Google Scholar 

  31. Turc-Carel, C., Philip, I., Berger, M. P., Philip, T., and Lenoir, G. M. Chromosome study of Ewing’s sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet. Cytogenet., 12: 1–19, 1984.

    Article  CAS  PubMed  Google Scholar 

  32. Turc-Carel, C., Aurias, A., Mugneret, F., Lizard, S., Sidaner, I., Volk, C., Thiery, J. P., Olschwang, S., Philip, I., Berger, M. P., and et al Chromosomes in Ewing’s sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12). Cancer Genet. Cytogenet., 32: 229–238, 1988.

    CAS  PubMed  Google Scholar 

  33. Ewen, M. E., Ludlow, J. W., Marsilio, E., DeCaprio, J. A., Millikan, R. C., Cheng, S. H., Paucha, E., and Livingston, D. M. An N-terminal transformation-governing sequence of SV40 large T antigen contributes to the binding of both p110Rb and a second cellular protein, p120. Cell, 58: 257–267, 1989.

    Article  CAS  PubMed  Google Scholar 

  34. Buckler, A. J., Chang, D. D., Graw, S. L., Brook, J. D., Haber, D. A., Sharp, P. A., and Housman, D. E. Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. Proc. Natl. Acad. Sci. U. S. A., 88: 4005–4009, 1991.

    CAS  PubMed  Google Scholar 

  35. Jeon, I. S., Davis, J. N., Braun, B. S., Sublett, J. E., Roussel, M. F., Denny, C. T., and Shapiro, D. N. A variant Ewing’s sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene, 10: 1229–1234, 1995.

    CAS  PubMed  Google Scholar 

  36. Peter, M., Couturier, J., Pacquement, H., Michon, J., Thomas, G., Magdelenat, H., and Delattre, O. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene, 14: 1159–1164, 1997.

    Article  CAS  PubMed  Google Scholar 

  37. Kaneko, Y., Yoshida, K., Handa, M., Toyoda, Y., Nishihira, H., Tanaka, Y., Sasaki, Y., Ishida, S., Higashino, F., and Fujinaga, K. Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes. Cancer, 15: 115–121, 1996.

    Article  CAS  PubMed  Google Scholar 

  38. Ishida, S., Yoshida, K., Kaneko, Y., Tanaka, Y., Sasaki, Y., Urano, F., Umezawa, A., Hata, J., and Fujinaga, K. The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma. Cytogenet. Cell Genet., 82: 278–283, 1998.

    Article  CAS  PubMed  Google Scholar 

  39. Dagher, R., Long, L. M., Read, E. J., Leitman, S. F., Carter, C. S., Tsokos, M., Goletz, T. J., Avila, N., Berzofsky, J. A., Helman, L. J., and Mackall, C. L. Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. Med. Pediatr. Oncol., 38: 158–164, 2002.

    Article  PubMed  Google Scholar 

  40. Hotfilder, M., Lanvers, C., Jurgens, H., Boos, J., and Vormoor, J. c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571). Cancer Chemother. Pharmacol., 50: 167–169, 2002.

    Article  CAS  PubMed  Google Scholar 

  41. Scotlandi, K., Manara, M. C., Strammiello, R., Landuzzi, L., Benini, S., Perdichizzi, S., Serra, M., Astolfi, A., Nicoletti, G., Lollini, P. L., Bertoni, F., Nanni, P., and Picci, P. C-kit receptor expression in Ewing’s sarcoma: lack of prognostic value but therapeutic targeting opportunities in appropriate conditions. J. Clin. Oncol., 21: 1952–1960, 2003.

    Article  CAS  PubMed  Google Scholar 

  42. Ye, D., Maitra, A., Timmons, C. F., Leavey, P. J., Ashfaq, R., and Ilaria Jr, R. L. The Epidermal Growth Factor Receptor HER2 Is Not a Major Therapeutic Target in Ewing Sarcoma. J. Pediatr. Hematol. Oncol., 25: 459–466, 2003.

    Article  PubMed  Google Scholar 

  43. Pedeutour, F., Simon, M. P., Minoletti, F., Sozzi, G., Pierotti, M. A., Hecht, F., and Turc-Carel, C. Ring 22 chromosomes in dermatofibrosarcoma protuberans are low-level amplifiers of chromosome 17 and 22 sequences. Cancer Res., 55: 2400–2403, 1995.

    CAS  PubMed  Google Scholar 

  44. Naeem, R., Lux, M. L., Huang, S. F., Naber, S. P., Corson, J. M., and Fletcher, J. A. Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am. J. Pathol., 147: 1553–1558, 1995.

    CAS  PubMed  Google Scholar 

  45. Simon, M. P., Pedeutour, F., Sirvent, N., Grosgeorge, J., Minoletti, F., Coindre, J. M., Terrier-Lacombe, M. J., Mandahl, N., Craver, R. D., Blin, N., Sozzi, G., Turc-Carel, C., O’Brien, K. P., Kedra, D., Fransson, I., Guilbaud, C., and Dumanski, J. P. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat. Genet., 15: 95–98, 1997.

    Article  CAS  PubMed  Google Scholar 

  46. Maki, R. G., Awan, R. A., Dixon, R. H., Jhanwar, S., and Antonescu, C. R. Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans. Int. J. Cancer, 100: 623–626, 2002.

    Article  CAS  PubMed  Google Scholar 

  47. Rubin, B. P., Schuetze, S. M., Eary, J. F., Norwood, T. H., Mirza, S., Conrad, E. U., and Bruckner, J. D. Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans. J. Clin. Oncol., 20: 3586–3591, 2002.

    Article  CAS  PubMed  Google Scholar 

  48. Alman, B. A., Li, C., Pajerski, M. E., Diaz-Cano, S., and Wolfe, H. J. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am. J. Pathol, 151: 329–334, 1997.

    CAS  PubMed  Google Scholar 

  49. Tejpar, S., Nollet, F., Li, C., Wunder, J. S., Michils, G., Dal Cin, P., Van Cutsem, E., Bapat, B., van Roy, F., Cassiman, J. J., and Alman, B. A. Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). Oncogene, 18: 6615–6620, 1999.

    Article  CAS  PubMed  Google Scholar 

  50. Fletcher, J. A., Naeem, R., Xiao, S., and Corson, J. M. Chromosome aberrations in desmoid tumors. Trisomy 8 may be a predictor of recurrence. Cancer Genet. Cytogenet., 79: 139–143, 1995.

    Article  CAS  PubMed  Google Scholar 

  51. Miyaki, M., Konishi, M., Kikuchi-Yanoshita, R., Enomoto, M., Tanaka, K., Takahashi, H., Muraoka, M., Mori, T., Konishi, F., and Iwama, T. Coexistence of somatic and germ-line mutations of APC gene in desmoid tumors from patients with familial adenomatous polyposis. Cancer Res., 53: 5079–5082, 1993.

    CAS  PubMed  Google Scholar 

  52. Sen-Gupta, S., Van der Luijt, R. B., Bowles, L. V., Meera Khan, P., and Delhanty, J. D. Somatic mutation of APC gene in desmoid tumour in familial adenomatous polyposis. Lancet, 342: 552–553, 1993.

    CAS  PubMed  Google Scholar 

  53. Mace, J., Sybil, B. J., Sondak, V., McGinn, C., Hayes, C., Thomas, D., and Baker, L. Response of extraabdominal desmoid tumors to therapy with imatinib mesylate. Cancer, 95: 2373–2379, 2002.

    Article  CAS  PubMed  Google Scholar 

  54. Schofield, D. E., Fletcher, J. A., Grier, H. E., and Yunis, E. J. Fibrosarcoma in infants and children. Application of new techniques. Am. J. Surg. Pathol., 18: 14–24, 1994.

    CAS  PubMed  Google Scholar 

  55. Schofield, D. E., Yunis, E. J., and Fletcher, J. A. Chromosome aberrations in mesoblastic nephroma. Am. J. Pathol., 143: 714–724, 1993.

    CAS  PubMed  Google Scholar 

  56. Knezevich, S. R., McFadden, D. E., Tao, W., Lim, J. F., and Sorensen, P. H. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat. Genet., 18: 184–187, 1998.

    Article  CAS  PubMed  Google Scholar 

  57. Rubin, B. P., Chen, C. J., Morgan, T. W., Xiao, S., Grier, H. E., Kozakewich, H. P., Perez-Atayde, A. R., and Fletcher, J. A. Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am. J. Pathol., 153: 1451–1458, 1998.

    CAS  PubMed  Google Scholar 

  58. Knezevich, S. R., Garnett, M. J., Pysher, T. J., Beckwith, J. B., Grundy, P. E., and Sorensen, P. H. ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res., 58: 5046–5048, 1998.

    CAS  PubMed  Google Scholar 

  59. Bolande, R. P. Congenital mesoblastic nephroma of infancy. Perspect. Pediatr. Pathol., 1: 227–250, 1973.

    CAS  PubMed  Google Scholar 

  60. Chung, E. B. and Enzinger, F. M. Infantile fibrosarcoma. Cancer, 38: 729–739, 1976.

    CAS  PubMed  Google Scholar 

  61. Treissman, S. P., Gillis, D. A., Lee, C. L., Giacomantonio, M., and Resch, L. Omental-mesenteric inflammatory pseudotumor. Cytogenetic demonstration of genetic changes and monoclonality in one tumor. Cancer, 73: 1433–1437, 1994.

    CAS  PubMed  Google Scholar 

  62. Snyder, C. S., Dell’Aquila, M., Haghighi, P., Baergen, R. N., Suh, Y. K., and Yi, E. S. Clonal changes in inflammatory pseudotumor of the lung: a case report. Cancer, 76: 1545–1549, 1995.

    CAS  PubMed  Google Scholar 

  63. Su, L. D., Atayde-Perez, A., Sheldon, S., Fletcher, J. A., and Weiss, S. W. Inflammatory myofibroblastic tumor: cytogenetic evidence supporting clonal origin. Mod. Pathol., 11: 364–368, 1998.

    CAS  PubMed  Google Scholar 

  64. Lawrence, B., Perez-Atayde, A., Hibbard, M. K., Rubin, B. P., Dal Cin, P., Pinkus, J. L., Pinkus, G. S., Xiao, S., Yi, E. S., Fletcher, C. D., and Fletcher, J. A. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am. J. Pathol, 157: 377–384, 2000.

    CAS  PubMed  Google Scholar 

  65. Rubin, B. P., Singer, S., Tsao, C., Duensing, A., Lux, M. L., Ruiz, R., Hibbard, M. K., Chen, C. J., Xiao, S., Tuveson, D. A., Demetri, G. D., Fletcher, C. D., and Fletcher, J. A. KIT Activation Is a Ubiquitous Feature of Gastrointestinal Stromal Tumors. Cancer Res., 61: 8118–8121, 2001.

    CAS  PubMed  Google Scholar 

  66. Heinrich, M. C., Corless, C. L., Duensing, A., McGreevey, L., Chen, C. J., Joseph, N., Singer, S., Griffith, D. J., Haley, A., Town, A., Demetri, G. D., Fletcher, C. D., and Fletcher, J. A. PDGFRA activating mutations in gastrointestinal stromal tumors. Science, 299: 708–710, 2003.

    Article  CAS  PubMed  Google Scholar 

  67. Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., Fletcher, J. A., Silverman, S. G., Silberman, S. L., Capdeville, R., Kiese, B., Peng, B., Dimitrijevic, S., Druker, B. J., Corless, C., Fletcher, C. D., and Joensuu, H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med., 347: 472–480, 2002.

    Article  CAS  PubMed  Google Scholar 

  68. van Oosterom, A. T., Judson, I., Verweij, J., Stroobants, S., Donato, d. P., Dimitrijevic, S., Martens, M., Webb, A., Sciot, R., Van Glabbeke, M., Silberman, S., and Nielsen, O. S. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet, 358: 1421–1423, 2001.

    PubMed  Google Scholar 

  69. Nishida, T., Hirota, S., Taniguchi, M., Hashimoto, K., Isozaki, K., Nakamura, H., Kanakura, Y., Tanaka, T., Takabayashi, A., Matsuda, H., and Kitamura, Y. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat. Genet., 19: 323–324, 1998.

    Article  CAS  PubMed  Google Scholar 

  70. Sarlomo-Rikala, M., el-Rifai, W., Lahtinen, T., Andersson, L. C., Miettinen, M., and Knuutila, S. Different patterns of DNA copy number changes in gastrointestinal stromal tumors, leiomyomas, and schwannomas. Hum. Pathol., 29: 476–481, 1998.

    CAS  PubMed  Google Scholar 

  71. Heinrich, M. C., Rubin, B. P., Longley, B. J., and Fletcher, J. A. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum. Pathol., 33: 484–495, 2002.

    Article  CAS  PubMed  Google Scholar 

  72. Legius, E., Marchuk, D. A., Collins, F. S., and Glover, T. W. Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat. Genet., 3: 122–126, 1993.

    Article  CAS  PubMed  Google Scholar 

  73. Basu, T. N., Gutmann, D. H., Fletcher, J. A., Glover, T. W., Collins, F. S., and Downward, J. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature, 356: 713–715, 1992.

    Article  CAS  PubMed  Google Scholar 

  74. DeClue, J. E., Papageorge, A. G., Fletcher, J. A., Diehl, S. R., Ratner, N., Vass, W. C., and Lowy, D. R. Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell, 69: 265–273, 1992.

    Google Scholar 

  75. Rouleau, G. A., Merel, P., Lutchman, M., Sanson, M., Zucman, J., Marineau, C., Hoang-Xuan, K., Demczuk, S., Desmaze, C., Plougastel, B., and et al Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature, 363: 515–521, 1993.

    Article  CAS  PubMed  Google Scholar 

  76. Twist, E. C., Ruttledge, M. H., Rousseau, M., Sanson, M., Papi, L., Merel, P., Delattre, O., Thomas, G., and Rouleau, G. A. The neurofibromatosis type 2 gene is inactivated in schwannomas. Hum. Mol. Genet., 3: 147–151, 1994.

    CAS  PubMed  Google Scholar 

  77. Lutchman, M. and Rouleau, G. A. The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Cancer Res., 55: 2270–2274, 1995.

    CAS  PubMed  Google Scholar 

  78. Kluwe, L., Friedrich, R., and Mautner, V.-F. Loss of NF1 allele in Schwann cells but not in fibroblasts dervied from an NF1-associated neurofibroma. Genes Chromosomes Cancer, 24: 283–285, 1999.

    Article  CAS  PubMed  Google Scholar 

  79. Xu, G. F., Lin, B., Tanaka, K., Dunn, D., Wood, D., Gesteland, R., White, R., Weiss, R., and Tamanoi, F. The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell, 63: 835–841, 1990.

    Article  CAS  PubMed  Google Scholar 

  80. Xu, G. F., O’Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R., and et al The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell, 62: 599–608, 1990.

    Article  CAS  PubMed  Google Scholar 

  81. Cox, A. D. and Der, C. J. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochim. Biophys. Acta, 1333: F51–F71, 1997.

    CAS  PubMed  Google Scholar 

  82. Cox, A. D. and Der, C. J. Ras family signaling: therapeutic targeting. Cancer Biol. Ther., 1: 599–606, 2002.

    CAS  PubMed  Google Scholar 

  83. Versteege, I., Sevenet, N., Lange, J., Rousseau-Merck, M. F., Ambros, P., Handgretinger, R., Aurias, A., and Delattre, O. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature, 394: 203–206, 1998.

    CAS  PubMed  Google Scholar 

  84. Biegel, J. A., Zhou, J. Y., Rorke, L. B., Stenstrom, C., Wainwright, L. M., and Fogelgren, B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res., 59: 74–79, 1999.

    CAS  PubMed  Google Scholar 

  85. Sevenet, N., Sheridan, E., Amram, D., Schneider, P., Handgretinger, R., and Delattre, O. Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am. J. Hum. Genet., 65: 1342–1348, 1999.

    CAS  PubMed  Google Scholar 

  86. Roberts, C. W., Galusha, S. A., McMenamin, M. E., Fletcher, C. D., and Orkin, S. H. Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc. Natl. Acad. Sci. U. S. A, 97: 13796–13800, 2000.

    Article  CAS  PubMed  Google Scholar 

  87. Galili, N., Davis, R. J., Fredericks, W. J., Mukhopadhyay, S., Rauscher, F. J. 3., Emanuel, B. S., Rovera, G., Barr, F. G., and Rauscher, F. J. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat. Genet., 5: 230–235, 1993.

    Article  CAS  PubMed  Google Scholar 

  88. Barr, F. G., Galili, N., Holick, J., Biegel, J. A., Rovera, G., and Emanuel, B. S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat. Genet., 3: 113–117, 1993.

    Article  CAS  PubMed  Google Scholar 

  89. Shapiro, D. N., Sublett, J. E., Li, B., Downing, J. R., and Naeve, C. W. Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res., 53: 5108–5112, 1993.

    CAS  PubMed  Google Scholar 

  90. Davis, R. J., D’Cruz, C. M., Lovell, M. A., Biegel, J. A., and Barr, F. G. Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res., 54: 2869–2872, 1994.

    CAS  PubMed  Google Scholar 

  91. Fredericks, W. J., Galili, N., Mukhopadhyay, S., Rovera, G., Bennicelli, J., Barr, F. G., Rauscher, F. J. 3., and Rauscher, F. J. r. The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3. Mol. Cell Biol., 15: 1522–1535, 1995.

    CAS  PubMed  Google Scholar 

  92. Bennicelli, J. L., Fredericks, W. J., Wilson, R. B., Rauscher, F. J. 3., and Barr, F. G. Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma contain potent, structurally distinct transcriptional activation domains. Oncogene, 11: 119–130, 1995.

    CAS  PubMed  Google Scholar 

  93. Sharp, R., Recio, J. A., Jhappan, C., Otsuka, T., Liu, S., Yu, Y., Liu, W., Anver, M., Navid, F., Helman, L. J., DePinho, R. A., and Merlino, G. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nat. Med., 8: 1276–1280, 2002.

    Article  CAS  PubMed  Google Scholar 

  94. Nanni, P., Nicoletti, G., De Giovanni, C., Croci, S., Astolfi, A., Landuzzi, L., Di Carlo, E., Iezzi, M., Musiani, P., and Lollini, P. L. Development of Rhabdomyosarcoma in HER-2/neu Transgenic p53 Mutant Mice. Cancer Res., 63: 2728–2732, 2003.

    CAS  PubMed  Google Scholar 

  95. Kalebic, T., Tsokos, M., and Helman, L. J. In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2. Cancer Res., 54: 5531–5534, 1994.

    CAS  PubMed  Google Scholar 

  96. Kalebic, T., Blakesley, V., Slade, C., Plasschaert, S., Leroith, D., and Helman, L. J. Expression of a kinase-deficient IGF-I-R suppresses tumorigenicity of rhabdomyosarcoma cells constitutively expressing a wild type IGF-I-R. Int. J. Cancer, 76: 223–227, 1998.

    Article  CAS  PubMed  Google Scholar 

  97. Clark, J., Rocques, P. J., Crew, A. J., Gill, S., Shipley, J., Chan, A. M., Gusterson, B. A., and Cooper, C. S. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat. Genet., 7: 502–508, 1994.

    Article  CAS  PubMed  Google Scholar 

  98. Matsuzaki, A., Suminoe, A., Hattori, H., Hoshina, T., and Hara, T. Immunotherapy with autologous dendritic cells and tumor-specific synthetic peptides for synovial sarcoma. J. Pediatr. Hematol. Oncol., 24: 220–223, 2002.

    Article  PubMed  Google Scholar 

  99. Allander, S. V., Illei, P. B., Chen, Y., Antonescu, C. R., Bittner, M., Ladanyi, M., and Meltzer, P. S. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am. J. Pathol., 161: 1587–1595, 2002.

    CAS  PubMed  Google Scholar 

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Fletcher, J.A. (2004). Molecular biology and cytogenetics of soft tissue sarcomas: Relevance for targeted therapies. In: Verweij, J., Pinedo, H.M. (eds) Targeting Treatment of Soft Tissue Sarcomas. Cancer Treatment and Research, vol 120. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7856-0_6

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