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The molecular pathogenesis of dedifferentiated chondrosarcoma

  • Symposium - Osteosarcoma
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Abstract

Dedifferentiated chondrosarcomas are cartilaginous tumors that consist of two distinguishable components, a lowgrade chondrosarcoma (chondrogenic) component and a highgrade dedifferentiated (anaplastic) component. The tumor cells in both components seem to originate from a single precursor, but there are a substantial number of genetic alterations in the anaplastic component. The underlying mechanism of dedifferentiation is unknown, but cell cycle regulators p16, p53 and retinoblastoma appear to have important roles in tumor development and dedifferentiation. In this article, molecular pathogenesis of dedifferentiated chondrosarcomas is reviewed.

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References

  1. Dorfman HD, Czerniak B. In: Year Book, editor. Bone Tumors. St. Louis, Missouri: Mosby; 1998. p. 395–410.

    Google Scholar 

  2. Dahlin DC, Beabout JW. Dedifferentiation of low-grade chondrosarcomas. Cancer 1971;28:461–6.

    Article  CAS  Google Scholar 

  3. Papagelopoulos PJ, Galanis EC, Mavrogenis AF, Savvidou OD, Bond JR, Unni KK, et al. Survivorship analysis in patients with periosteal chondrosarcoma. Clin Orthop Relat Res 2006;448:199–207.

    Article  Google Scholar 

  4. Frassica FJ, Unni KK, Beabout JW, Sim FH. Dedifferentiated chondrosarcoma. A report of the clinicopathological features and treatment of seventy-eight cases. Dedifferentiated chondrosarcoma 1986;68:1197–205.

    CAS  Google Scholar 

  5. Mercuri M, Picci P, Campanacci L, Rulli E. Dedifferentiated chondrosarcoma. Skeletal Radiol 1995;24:409–16.

    Article  CAS  Google Scholar 

  6. Dickey ID, Rose PS, Fuchs B, Wold LE, Okuno SH, Sim FH, et al. Dedifferentiated chondrosarcoma: The role of chemotherapy with updated outcomes. J Bone Joint Surg Am 2004;86-A:2412–8.

    Article  Google Scholar 

  7. Bruns J, Fiedler W, Werner M, Delling G. Dedifferentiated chondrosarcoma - A fatal disease. J Cancer Res Clin Oncol 2005;131:333–9.

    Article  CAS  Google Scholar 

  8. Grimer RJ, Gosheger G, Taminiau A, Biau D, Matejovsky Z, Kollender Y, et al. Dedifferentiated chondrosarcoma: Prognostic factors and outcome from a European group. Eur J Cancer 2007;43:2060–5.

    Article  Google Scholar 

  9. Capanna R, Bertoni F, Bettelli G, Picci P, Bacchini P, Present D, et al. Dedifferentiated chondrosarcoma. J Bone Joint Surg Am 1988;70:60–9.

    Article  CAS  Google Scholar 

  10. Dornauer K, Söder S, Inwards CY, Bovee JV, Aigner T. Matrix biochemistry and cell biology of dedifferentiated chondrosarcomas. Pathol Int 2010;60:365–72.

    Article  Google Scholar 

  11. Simms WW, Ordóñez NG, Johnston D, Ayala AG, Czerniak B. p53 expression in dedifferentiated chondrosarcoma. Cancer 1995;76:223–7.

    Article  CAS  Google Scholar 

  12. Yang L, Chen Q, Zhang S, Wang X, Li W, Wen J, et al. A novel mutated cell line with characteristics of dedifferentiated chondrosarcoma. Int J Mol Med 2009;24:427–35.

    Article  CAS  Google Scholar 

  13. Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 2005;93:631–40.

    Article  CAS  Google Scholar 

  14. Häckel C, Czerniak B, Ayala AG, Radig K, Roessner A. Expression of plasminogen activators and plasminogen activator inhibitor in dedifferentiated chondrosarcoma. Cancer 1997;79:53–8.

    Article  Google Scholar 

  15. Rozeman LB, de Bruijn IH, Bacchini P, Staals EL, Bertoni F, Bovée JV, et al. Dedifferentiated peripheral chondrosarcomas: Regulation of EXT-downstream molecules and differentiation-related genes. Mod Pathol 2009;22:1489–98.

    Article  CAS  Google Scholar 

  16. Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, et al. Matrix metalloproteinases: A review. Crit Rev Oral Biol Med 1993;4:197–250.

    Article  CAS  Google Scholar 

  17. Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M. Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma. J Cancer Res Clin Oncol 1999;125:541–8.

    Article  CAS  Google Scholar 

  18. van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, et al. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: A report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 2010;16:1597–604.

    Article  Google Scholar 

  19. Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F, et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 2011;224:334–43.

    Article  CAS  Google Scholar 

  20. Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF. The molecular pathogenesis of osteosarcoma: A review. Sarcoma 2011;2011:959248.

    Article  Google Scholar 

  21. Morrison C, Radmacher M, Mohammed N, Suster D, Auer H, Jones S, et al. MYC amplification and polysomy 8 in chondrosarcoma: Array comparative genomic hybridization, fluorescent in situ hybridization and association with outcome. J Clin Oncol 2005;23:9369–76.

    Article  CAS  Google Scholar 

  22. Sakamoto A, Oda Y, Adachi T, Oshiro Y, Tamiya S, Tanaka K, et al. H-ras oncogene mutation in dedifferentiated chondrosarcoma: Polymerase chain reaction-restriction fragment length polymorphism analysis. Mod Pathol 2001;14:343–9.

    Article  CAS  Google Scholar 

  23. Bridge JA, DeBoer J, Travis J, Johansson SL, Elmberger G, Noel SM, et al. Simultaneous interphase cytogenetic analysis and fluorescence immunophenotyping of dedifferentiated chondrosarcoma. Implications for histopathogenesis. Simultaneous interphase cytogenetic analysis and fluorescence immunophenotyping of dedifferentiated chondrosarcoma 1994;144:215–20.

    CAS  Google Scholar 

  24. Bovée JV, Cleton-Jansen AM, Rosenberg C, Taminiau AH, Cornelisse CJ, Hogendoorn PC. Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis. J Pathol 1999;189:454–62.

    Article  Google Scholar 

  25. Röpke M, Boltze C, Neumann HW, Roessner A, Schneider-Stock R. Genetic and epigenetic alterations in tumor progression in a dedifferentiated chondrosarcoma. Pathol Res Pract 2003;199:437–44.

    Article  Google Scholar 

  26. Sanerkin NG, Woods CG. Fibrosarcomata and malignant fibrous histiocytomata arising in relation to enchondromata. J Bone Joint Surg Br 1979;61-B:366–72.

    Article  CAS  Google Scholar 

  27. Swarts SJ, Neff JR, Johansson SL, Bridge JA. Cytogenetic analysis of dedifferentiated chondrosarcoma. Cancer Genet Cytogenet 1996;89:49–51.

    Article  CAS  Google Scholar 

  28. Sawyer JR, Swanson CM, Lukacs JL, Nicholas RW, North PE, Thomas JR. Evidence of an association between 6q13-21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors. Cancer 1998;82:474–83.

    Article  CAS  Google Scholar 

  29. Hallor KH, Staaf J, Bovée JV, Hogendoorn PC, Cleton-Jansen AM, Knuutila S, et al. Genomic profiling of chondrosarcoma: Chromosomal patterns in central and peripheral tumors. Clin Cancer Res 2009;15:2685–94.

    Article  CAS  Google Scholar 

  30. O’Malley DP, Opheim KE, Barry TS, Chapman DB, Emond MJ, Conrad EU, et al. Chromosomal changes in a dedifferentiated chondrosarcoma: A case report and review of the literature. Cancer Genet Cytogenet 2001;124:105–11.

    Article  Google Scholar 

  31. Hameed M, Ulger C, Yasar D, Limaye N, Kurvathi R, Streck D, et al. Genome profiling of chondrosarcoma using oligonucleotide array-based comparative genomic hybridization. Cancer Genet Cytogenet 2009;192:56–9.

    Article  CAS  Google Scholar 

  32. Asp J, Sangiorgi L, Inerot SE, Lindahl A, Molendini L, Benassi MS, et al. Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues. Int J Cancer 2000;85:782–6.

    Article  CAS  Google Scholar 

  33. Terek RM, Healey JH, Garin-Chesa P, Mak S, Huvos A, Albino AP. p53 mutations in chondrosarcoma. Diagn Mol Pathol 1998;7:51–6.

    Article  CAS  Google Scholar 

  34. Dobashi Y, Sugimura H, Sato A, Hirabayashi T, Kanda H, Kitagawa T, et al. Possible association of p53 overexpression and mutation with high-grade chondrosarcoma. Diagn Mol Pathol 1993;2:257–63.

    Article  CAS  Google Scholar 

  35. Röpke M, Boltze C, Meyer B, Neumann HW, Roessner A, Schneider-Stock R. Rb-loss is associated with high malignancy in chondrosarcoma. Oncol Rep 2006;15:89–95.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Akio Sakamoto

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  1. Akio Sakamoto
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Correspondence to Akio Sakamoto.

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Sakamoto, A. The molecular pathogenesis of dedifferentiated chondrosarcoma. IJOO 48, 262–265 (2014). https://doi.org/10.4103/0019-5413.132506

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  • DOI: https://doi.org/10.4103/0019-5413.132506

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