Abstract
This chapter presents cytogenetic and molecular pathology of sarcomas, with emphasis on recurrent abnormalities that are characteristic features of individual cancer types. General concepts concerning biology, pathology, diagnostic techniques, and molecular diagnostic applications of cancers are presented in the beginning of the chapter. The second portion presents each of the major sarcoma types, in alphabetical order, with a specific structure: basic pathology, clinical features, molecular genetic pathology, and molecular diagnosis. Most of the tumors presented herein are soft tissue sarcomas, as few recurrent abnormalities have been established to have biologic and diagnostic significance in bone tumors. In contrast to other diseases and cancers presented in this textbook, sarcomas are more commonly associated with cytogenetic changes, as opposed to molecular changes. Nevertheless, a variety of approaches (e.g., classical cytogenetic analysis, fluorescence in situ hybridization, reverse-transcriptase polymerase chain reaction, immunohistochemistry) are presented, with strengths and weaknesses of each for clinical application in each tumor type, as appropriate.
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Antonescu CR. The role of genetic testing in soft tissue sarcoma. Histopathology. 2006;48:13–21.
Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356–62.
Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, et al. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007;46:1051–60.
Antonescu CR, Zhang L, Chang N, Pawel BR, Travis W, Rosenberg AE, et al. Novel EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of 66 cases, including soft tissue, bone and visceral lesions, showing common involvement of EWSR1 gene rearrangement. Genes Chromosomes Cancer. 2010;49:1114–24.
Antonescu CR, Zhang L, Nielsen P, Rosenberg A, Dal Cin P, Fletcher CD. Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer. 2011;50:757–64.
Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27:750–61.
Atlas of Genetics and Cytogenetics in Oncology and Haematology, http://www.infobiogen.fr/services/chromcancer/index.html. Barr FG, Ladanyi M. Sarcomas. In: Leonard DGB, editor. Diagnostic molecular pathology. Philadelphia: Saunders; 2003, p. 53–76.
Barr FG, Womer RB. Molecular diagnosis of ewing family tumors: too many fusions… ? J Mol Diagn. 2007;9:437–40.
Bovée JV, Hogendoorn PC. Molecular pathology of sarcomas: concepts and clinical implications. Virchows Arch. 2010;456:193–9.
Breitfield PP, Meyer WH. Rhabdomyosarcoma: new windows of opportunity. Oncologist. 2005;10:518–27.
Chang CC, Shidham VB. Molecular genetics of pediatric soft tissue tumors. J Mol Diagn. 2003;5:143–54.
Fisher C. Soft tissue sarcomas with non-EWS translocations: molecular genetic features and pathologic and clinical correlations. Virchows Arch. 2010;456:153–66.
Guillou L, Benhattar J, Bonichon F, et al. Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol. 2004;22:4040–50.
Jain S, Xu R, Prieto VG, Lee P. Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol. 2010;3:416–28.
Lee CH, Ou W, Marino-Enriquez A, Zhu M, Myeda M, Wang YX, et al. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci USA. 2012;109:929–34.
Lemm D, Mügge LO, Mentzel T, Höffken K. Current treatment options in dermatofibrosarcoma protuberans. J Cancer Res Clin Oncol. 2009;135:653–65.
Lessnick SL, Kovar H, Houghton P. The molecular basis of sarcoma. Sarcoma. 2011;2011:864130.
Mariño-Enríquez A, Wang WL, Roy A, Lopez-Terrada D, Lazar AJ, Fletcher CD, et al. Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol. 2011;35:135–44.
Mertens F, Fletcher CD, Antonescu CR, et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest. 2005;85:408–15.
O’Leary TJ, Frisman DM. Soft tissue and bones. In: O’Leary TJ, editor. Advanced diagnostic methods in pathology. Saunders: Philadelphia; 2003. p. 421–58.
Ordóñez JL, Osuna D, García-Domínguez DJ, Amaral AT, Otero-Motta AP, Mackintosh C, et al. The clinical relevance of molecular genetics in soft tissue sarcomas. Adv Anat Pathol. 2010;17:162–81.
Romeo S, Dei Tos AP. Soft tissue tumors associated with EWSR1 translocation. Virchows Arch. 2010;456:219–34.
Romeo S, Dei Tos AP. Clinical application of molecular pathology in sarcomas. Curr Opin Oncol. 2011;23:379–84.
Sankar S, Lessnick SL. Promiscuous partnerships in Ewing’s sarcoma. Cancer Genet. 2011;204:351–65.
Sorensen PHB, Lynch JC, Qualman SJ, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children’s oncology group. J Clin Oncol. 2002;20:2672–9.
Storlazzi CT, Mertens F, Nascimento A, et al. Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. Hum Mol Genet. 2003;12:2349–58.
Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ. Hogendoorn PC The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology. Clin Cancer Res. 2009;15(7):2259–68.
Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A, Meloni-Ehrig A, et al. Recurrent (2;2) and (2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator (NCOA) family. Genes Chromosomes Cancer. 2010;49:224–36.
Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, et al. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med. 2011;3(98):98ra82.
Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M. Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer. 2011;11(8):541–57.
Wang L, Motoi T, Khanin R, Socci N, Olshen A, Mertens F, et al. Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer. 2012;51:127–39.
Williamson D, Lu YJ, Gordon T, et al. Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype. J Clin Oncol. 2005;23:880–8.
Xia SJ, Barr FG. Chromosome translocations in sarcomas and the emergence of oncogenic transcription factors. Eur J Cancer. 2005;41:2513–27.
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Lindeman, N.I., Cin, P.D. (2013). Molecular Pathology of Soft Tissue and Bone Tumors. In: Cheng, L., Eble, J. (eds) Molecular Surgical Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4900-3_15
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DOI: https://doi.org/10.1007/978-1-4614-4900-3_15
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