Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-09T09:04:13.567Z Has data issue: false hasContentIssue false

Chap 4 - GENETICS OF SOFT TISSUE TUMORS

Published online by Cambridge University Press:  01 March 2011

By
Julia A. Bridge  and
Marilu Nelson
Edited by
Markku Miettinen
Markku Miettinen
Affiliation:
Armed Forces Institute of Pathology, Washington DC
Get access

Summary

The evolution of mesenchymal tumor classification schemes has coincided with cytogenetic and molecular advances. Increasing recognition of the specific genetic abnormalities inherent in these tumors and the growing use of cytogenetic and molecular genetic procedures have aided in the formulation of a diagnosis and the resolution of cellular origin. Several of the genetic markers are also of prognostic value, and the importance of molecular testing for guiding targeted therapeutic strategies in mesenchymal neoplasia is emerging.

The objective of this chapter is to review recurrent or tumor-specific genetic events in mesenchymal neoplasms and discuss the cytogenetic and molecular cytogenetic approaches commonly used in clinical practice to identify them.

GENETIC EVENTS AND MOLECULAR PATHOLOGIC APPROACHES

Three common genetic approaches used to identify mesenchymal tumor-specific abnormalities include (1) conventional cytogenetic; (2) molecular cytogenetic (fluorescence in situ hybridization [FISH]); and, (3) reverse transcription-polymerase chain reaction (RT-PCR) analyses. Historically, many of the genetic abnormalities that have come to be recognized as tumor specific in sarcomas were first identified by conventional cytogenetic analysis. In turn, the initial cytogenetic evidence facilitated the cloning of many candidate genes involved in the pathogenesis of mesenchymal tumors. Cytogenetic analysis has provided clinicians with a valuable tool to supplement their diagnostic armamentarium. The addition of molecular cytogenetic (FISH) and molecular approaches (RT-PCR) has further enhanced the sensitivity and accuracy of detecting nonrandom chromosomal imbalances or structural rearrangements in sarcomas, including assessment in formalin-fixed, paraffin-embedded tissues.

Type
Chapter
Information
Modern Soft Tissue Pathology
Tumors and Non-Neoplastic Conditions
 , pp. 105 - 126
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Sandberg, AA, Bridge, JA. The Cytogenetics of Bone and Soft Tissue Tumors. Austin: RG Landes, CRC Press, 1994.Google Scholar
Fletcher, JA, Kozakewich, HP, Hoffer, FA, Lage, JM, Wiedner, N, Tepper, R. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med 1991;324:436–442.CrossRefGoogle ScholarPubMed
Dal Cin, P. Metaphase harvest and cytogenetic analysis of malignant hematological specimens. Current Protocols in Human Genetics. 2003 May, Chapter 10: Unit 10.2.
Mandahl, N. Methods in solid tumour cytogenetics. In: Rooney, , eds. Human Cytogenetics. A Practical Approach. Volume II. Malignancy and Acquired Abnormalities, 3rd ed. Oxford: Oxford University Press, 2001: 165–203.Google Scholar
Thompson, FH. Cytogenetic methods and findings in human solid tumors. In: Brach, MJ, Knutsen, T, Spurbeck, J, eds. The AGT Cytogenetics Laboratory Manual, 3rd ed. Philadelphia: Lippincott-Raven, 1997:375–430.
Freshney, RI. Culture of Tumor Cells. In: Culture of Animal Cells: A Manual of Basic Techniques, 5th ed. Hoboken, , New Jersey: John Wiley & Sons, Inc.; 2005. Chapter 24: 421–433.
Wang, HC, Federoff, S. Banding in human chromosomes treated with trypsin. Nature New Biol 1972;235:52–53.CrossRefGoogle ScholarPubMed
Seabright, M. A rapid banding technique for human chromosomes. Lancet 1971;2:971–972.CrossRefGoogle ScholarPubMed
Yunis, JJ. New chromosome techniques in the study of human neoplasia. Hum Pathol 1981;12:540–549.CrossRefGoogle Scholar
Shaffer, LG, Tommerup, N. Ed. ISCN (2005 An International System for Human Cytogenetic Nomenclature. Basel: S. Karger;2005.Google Scholar
,Denver Conference: A proposed standard system on nomenclature of human mitotic chromosomes. Lancet 1960;i:1063–1065.Google Scholar
,Paris Conference (1971: Standardization in human cytogenetics. Birth Defects Orig Artic Ser 1972;8:1–46.Google Scholar
Bridge, JA. Advantages and limitations of cytogenetic, molecular cytogenetic, and molecular diagnostic testing in mesenchymal neoplasms. J Orthop Sci 2008;13:273–282.CrossRefGoogle ScholarPubMed
Pinkel, D, Gray, J, Trask, B, Engh, G, Fuscoe, J, Dekken, H. Cytogenetic analysis by in situ hybridization with fluorescently labeled nucleic acid probes. Cold Spring Harbor Symp Quant Biol 1986;51:151–157.CrossRefGoogle ScholarPubMed
Speicher, MR, Gwyn Ballard, S, Ward, DC. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet 1996;12:368–375.CrossRefGoogle ScholarPubMed
Schröck, E, du Manoir, S, Veldman, T, Schoell, B, Wienberg, J, Ferguson-Smith, MA. Multicolor spectral karyotyping of human chromosomes. Science 1996;273:494–497.CrossRefGoogle ScholarPubMed
Tanke, HJ, Wiegant, J, Gijlswijk, RP, Bezrookove, V, Pattenier, H, Heetebrij, RJ. New strategy for multi-colour fluorescence in situ hybridization: COBRA: Combined binary ratio labelling. Eur J Hum Genet 1999;7:2–11.CrossRefGoogle ScholarPubMed
Kallioniemi, A, Kallioniemi, OP, Sudar, D, Rutovitz, D, Gray, JW, Waldman, F. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 1992;258:818–821.CrossRefGoogle ScholarPubMed
Pinkel, D, Segraves, R, Sudar, D, Clark, S, Poole, I, Kowbel, D. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 1998;20:207–211.CrossRefGoogle ScholarPubMed
Solinas-Toldo, S, Lampel, S, Stilgenbauer, S, Nickolenko, J, Benner, A, Dohner, H. Matrix-based comparative genomic hybridization: Biochips to screen for genomic imbalances. Genes Chromosomes Cancer 1997;20:399–407.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Mundle, SD, Koska, RJ. Fluorescence In Hybridization, Situ. A Major Milestone in Luminous Cytogenetics. Molecular Diagnostics: For the Clinical Laboratorian, 2nd ed. Coleman, W.B. and Tsongalis, G.J. eds. Totowa, NJ: Humana Press, 2006:196.Google Scholar
Jabs, EW, Wolf, SF, Migeon, BR. Characterization of a cloned DNA sequence that is present at centromeres of all human autosomes and the X chromosome and shows polymorphic variation. Proc Natl Acad Sci USA 1984;81:4882–4888.CrossRefGoogle ScholarPubMed
Guan, XY, Meltzer, P, Trent, J. Rapid generation of whole chromosome painting probes (WCPs) by chromosome microdissection. Genomics 1994;22:101–107.CrossRefGoogle ScholarPubMed
Lichter, P, Ledbetter, SA, Ledbetter, DH, Ward, DC. Fluorescence in situ hybridization with ALU and L1 polymerase chain reaction probes for rapid characterization of human chromosomes in hybrid cell lines. Proc Natl Acad Sci USA 1990;85:9138–9142.Google Scholar
Ladanyi, M, Bridge, JA. Contribution of molecular genetic data to the classification of sarcomas. Hum Pathol 2000;31:532–538.CrossRefGoogle ScholarPubMed
Sandberg, AA, Bridge, JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: clear cell sarcoma (malignant melanoma of soft parts). Cancer Genet Cytogenet 2001;130:1–7.CrossRefGoogle Scholar
Patel, RM, Downs-Kelly, E, Weiss, SW, Folpe, AL, Tubbs, RR, Tuthill, RJ. Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma. Mod Pathol 2005;18:1585–1590.CrossRefGoogle ScholarPubMed
http://www.acmg.net/Pages/ACMG_Activities/stds-(2002/e.htm.
Weiss, LM, Chen, YY. Effects of different fixatives on detection of nucleic acids from paraffin-embedded tissues by in situ hybridization using oligonucleotide probes. J Histochem Cytochem 1991;30:1237–1241.CrossRefGoogle Scholar
Watters, AD, Bartlett, JM. Fluorescence in situ hybridization in paraffin tissue sections: pretreatment protocol. Mol Biotechnol 2002;21:217–220.CrossRefGoogle ScholarPubMed
Kearney, L, Hammond, DW. Molecular cytogenetic technologies. In: Rooney, , eds. Human Cytogenetics. A Practical Approach. Volume II. Malignancy and Acquired Abnormalities, 3rd ed. Oxford: Oxford University Press, 2001:129–163.Google Scholar
Schwab, M, Shimada, H, Joshi, V, Brodeur, GM: Neuroblastic tumours of adrenal gland and sympathetic nervous system. World Health Organization Classification of Tumours: Pathology & Genetics. Tumours of the Nervous System. Edited by Kleinhues, P, Cavenee, WK. Lyon: IARC Press, 2000:159.Google Scholar
Fluorescence in situ hybridization: Technical overview. In Molecular Diagnosis of Cancer: Methods and Protocols, 2nd ed. Roulston, JE, Bartlett, JMS eds. Totowa, NJ: Humana Press, 2004:77–87.CrossRef
Sandberg, AA. Cytogenetics and molecular genetics of bone and soft-tissue tumors. Am J Med Genet 2002;115:189–193.CrossRefGoogle ScholarPubMed
Dewald, GW. Interphase FISH studies of chronic myeloid leukemia. Methods Mol Biol 2002;204:311–342.Google ScholarPubMed
Weber-Matthiesen, K, Winkemann, M, Müller-Hermelink, A, Schlegelberger, B, Grote, W. Simultaneous fluorescence immunophenotyping and interphase cytogenetics: a contribution to the characterization of tumor cells. J Histochem Cytochem 1992;40:171–175.CrossRefGoogle ScholarPubMed
Perry, A, Roth, KA, Banerjee, R, Fuller, CE, Gutmann, DH. NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. Am J Pathol 2001;159:57–61.CrossRefGoogle ScholarPubMed
Bridge, JA, Fidler, ME, Neff, JR, Degenhardt, J, Wang, M, Walker, C. Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift. Am J Surg Pathol 1999;23:159–165.CrossRefGoogle ScholarPubMed
Summersgill, B, Clark, J, Shipley, J. Fluorescence and chromogenic in situ hybridization to detect genetic aberrations in formalin-fixed paraffin embedded material, including tissue microarrays. Nat Protoc 2008;3:220–234.CrossRefGoogle ScholarPubMed
Dandachi, N, Dietze, O, Hauser-Kronberger, C. Chromogenic in situ hybridization: A novel approach to a practical and sensitive method for the detection of HER2 oncogene in archival human breast carcinoma. Lab Invest 2002 Aug;82(8):1007–1014.CrossRefGoogle ScholarPubMed
Speicher, MR, Carter, NP. The new cytogenetics: blurring the boundaries with molecular biology. Nat Rev Genet 2005;6:782–792.CrossRefGoogle ScholarPubMed
Wiegant, J, Bezrookove, V, Rosenberg, C, Tanke, HJ, Raap, AK, Zhang, H. Differentially painting human chromosome arms with combined binary ratio-labeling fluorescence in situ hybridization. Genome Res 2000 Jun;10(6):861–865.CrossRefGoogle ScholarPubMed
Kallioniemi, A, Kallioniemi, OP, Sudar, D, Rutovitz, D, Gray, JW, Waldman, F. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 1992;258:818.CrossRefGoogle ScholarPubMed
Kallioniemi, OP, Kallioniemi, A, Piper, J, Isola, J, Waldman, FM, Gray, JW. Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors. Genes Chromosomes Cancer 1994;10:231–243.CrossRefGoogle ScholarPubMed
Pinkel, D, Albertson, DG. Comparative genomic hybridization. Annu Rev Genomics Hum Genet 2005;6:331.CrossRefGoogle ScholarPubMed
Cowell, JK, Hawthorn, L. The application of microarray technology to the analysis of the cancer genome. Curr Mol Med 2007;7:103–120.CrossRefGoogle ScholarPubMed
Nielsen, TO. Microarray analysis of sarcomas. Adv Anat Pathol 2006 Jul;13(4):166–173.CrossRefGoogle ScholarPubMed
West, RB, Rijn, M. The role of microarray technologies in the study of soft tissue tumours. Histopathology 2006;48:22–31.CrossRefGoogle Scholar
Sakabe, T, Shinomiya, T, Mori, T, Ariyama, Y, Fukuda, Y, Fujiwara, T. Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization. Cancer Res 1999;59:511–515.Google ScholarPubMed
Bridge, JA, Liu, J, Qualman, SJ, Suijkerbuijk, R, Wenger, G, Zhang, J. Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplifications predominates in embryonal with anaplasia and alveolar subtypes. Genes Chromosomes Cancer 2002;33:310–321.CrossRefGoogle Scholar
Albertson, DG. Gene amplification in cancer. Trends Genet 2006;22:447–55.CrossRefGoogle Scholar
Sirvent, N, Coindre, JM, Maire, G, Hostein, I, Keslair, F, Guillou, L. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol 2007;31:1476–1489.CrossRefGoogle ScholarPubMed
Binh, MB, Sastre-Garau, X, Guillou, L, Pinieux, G, Terrier, P, Lagacé, R. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol 2005;29:1340–1347.CrossRefGoogle ScholarPubMed
Weaver, J, Goldblum, JR, Turner, S, Tubbs, RR, Wang, WL, Lazar, AJ. Detection of MDM2 gene amplification or protein expression distinguishes sclerosing mesenteritis and retroperitoneal fibrosis from inflammatory well-differentiated liposarcoma. Mod Pathol 2009;22:66–70.CrossRefGoogle ScholarPubMed
Nowell, P, Hungerford, D. A minute chromosome in chronic granulocytic leukemia. Science 1960;1332:1947.Google Scholar
Aurias, A, Rimbaut, C, Buffe, D, Dubousset, J, Mazabraud A. Translocation of chromosome 22 in Ewing's sarcoma. CR Seances Acad Sci III: 1983;296:1105–1107.Google ScholarPubMed
Delattre, O, Zucman, J, Melot, T, Garau, XS, Zucker, JM, Lenoir, GM. The Ewing family of tumors – a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994;331:294–299.CrossRefGoogle ScholarPubMed
Fletcher, CD, Busam, KJ. The clinical role of molecular genetics in soft tissue tumor pathology. Cancer Metastasis Rev 1997;16:207–227.Google Scholar
Antonescu, CR. The role of genetic testing in soft tissue sarcoma. Histopathology 2006;48:13–21.CrossRefGoogle ScholarPubMed
Ladanyi, M, Antonescu, CR, Dal Cin, P. Cytogenetic and molecular genetic pathology of soft tissue tumors. In: Enzinger and Weiss's Soft Tissue Tumors. Weiss, SW, Goldblum, JR, editors. Philadelphia: Mosby Elsevier Inc., 2008:73–102.Google Scholar
Bridge, JA. Contribution of cytogenetics to the management of poorly differentiated sarcomas. Ultrastruct Pathol 2008;32:63–71.CrossRefGoogle ScholarPubMed
Polito, P, Dal Cin, P, Sciot, R, Brock, P, Eykan, P, Berghe, H. Embryonal rhabdomyosarcoma with only numerical chromosome changes. Case report and review of the literature. Cancer Genet Cytogenet 1999;109:161–165.CrossRefGoogle ScholarPubMed
Bridge, JA, Liu, J, Weibolt, V, Baker, KS, Perry, D, Kruger, R. Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study. Genes Chromosomes Cancer 2000; 27:337–344.3.0.CO;2-1>CrossRefGoogle Scholar
Plaat, BE, Molenaar, WM, Mastik, MF, Hoekstra, HJ, te Meerman, GJ, Berg, E. Computer-assisted cytogenetic analysis of 51 malignant peripheral nerve sheath tumors: sporadic vs. neurofibromatosis-type-1-associated malignant schwannomas. Int J Cancer 1999;83:171–178.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Mertens, F, Dal Cin, P, Wever, I, Fletcher, CD, Mandahl, N, Mitelman, F. Cytogenetic characterization of peripheral nerve sheath tumours: a report of the CHAMP study group. J Pathol 2000;190:31–38.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Bridge, RS Jr, Bridge, JA, Neff, JR, Naumann, S, Althof, P, Bruch, . Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study. J Clin Pathol 2004;57:1172–1178.CrossRefGoogle ScholarPubMed
Borden, EC, Baker, LH, Bell, RS, Bramwell, V, Demetri, GD, Eisenberg, BL. Soft tissue sarcomas of adults: state of the translational science. Clin Cancer Res 2003;9:1941–1956.Google ScholarPubMed
Deneen, B, Denny, CT. Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation. Oncogene 2001;20:6731–6741.CrossRefGoogle ScholarPubMed
Lessnick, SL, Dacwag, CS, and Golub, TR. The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts. Cancer Cell 2002;1:393–401.CrossRefGoogle ScholarPubMed
Xia, SJ, Barr, FG. Chromosome translocations in sarcomas and the emergence of oncogenic transcription factors. Eur J Cancer 2005;41:2513–2527.CrossRefGoogle ScholarPubMed
Mugneret, F, Lizard, S, Aurias, A, Turc-Carel, C. Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet 1988;32:239–245.CrossRefGoogle Scholar
Höglund, M, Gisselsson, D, Mandahl, N, Mitelman, F. Ewing tumours and synovial sarcomas have critical features of karyotype evolution in common with epithelial tumours. Int J Cancer 2005;116:401–406.CrossRefGoogle ScholarPubMed
Skytting, BT, Szymanska, J, Aalto, Y, Lushnikova, T, Blomqvist, C, Elomaa, I. Clinical importance of genomic imbalances in synovial sarcoma evaluated by comparative genomic hybridization. Cancer Genet Cytogenet 1999;115:39–46.CrossRefGoogle ScholarPubMed
Hattinger, CM, Rumpler, S, Ambros, IM, Strehl, S, Lion, T, Zoubek, A. Demonstration of the translocation der(16)t(1;16)(q12;q11.2) in interphase nuclei of Ewing tumors. Genes Chromosomes Cancer 1996;17:141–150.3.0.CO;2-4>CrossRefGoogle Scholar
Stark, B, Mor, C, Jeison, M, Gobuzov, R, Cohen, IJ, Goshen, Y. Additional chromosome 1q aberrations and der(16)t(1;16), correlation to the phenotypic expression and clinical behavior of the Ewing family of tumors. J Neurooncol 1997;31:3–8.CrossRefGoogle Scholar
Sandberg, AA, Bridge, JA. Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumors. Cancer Genet Cytogenet 2000;123:1–26.CrossRefGoogle ScholarPubMed
Hirota, S, Isozaki, K, Moriyama, Y, Hashimoto, K, Nishida, T, Ishiguro, S. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279: 577–580.CrossRefGoogle ScholarPubMed
Hirota, S, Ohashi, A, Nishida, T, Isozaki, K, Kinoshita, K, Shinomura, Y. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 2003;125:660–667.CrossRefGoogle ScholarPubMed
Lasota, J, Dansonka-Mieszkowska, A, Sobin, LH, Miettinen, M. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004;84:874–883.CrossRefGoogle ScholarPubMed
Delattre, O, Zucman, J, Plougastel, B, Desmaze, C, Melot, T, Peter, M. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992;359:162–165.CrossRefGoogle ScholarPubMed
Zucman, J, Melot, T, Desmaze, C, Ghysdael, J, Plougastel, B, Peter, M. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J 1993;12:4481–4487.Google ScholarPubMed
Jeon, IS, Davis, JN, Braun, BS, Sublett, JE, Roussel, MF, Denny, CT. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 1995;10:1229–1234.Google ScholarPubMed
Kaneko, Y, Yoshida, K, Handa, M, Toyoda, Y, Nishihara, H, Tanaka, Y. 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 1996;15:115–121.3.0.CO;2-6>CrossRefGoogle Scholar
Peter, M, Couturier, J, Pacquement, H, Michon, J, Thomas, G, Magdelenat, H. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 1997;14:1159–1164.CrossRefGoogle ScholarPubMed
Mastrangelo, T, Modena, P, Tornielli, S, Bullrich, F, Testi, MA, Mezzelani, A. A novel zinc finger gene is fused to EWS in small round cell tumor. Oncogene 2000;19:3799–3804.CrossRefGoogle ScholarPubMed
Wang, L, Bhargava, R, Zheng, T, Wexler, L, Collins, MH, Roulston, D. Undifferentiated small round cell sarcomas with rare EWS gene fusions: identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions. J Mol Diagn 2007;9:498–509.CrossRefGoogle ScholarPubMed
Shing, DC, McMullan, DJ, Roberts, P, Smith, K, Chin, SF, Nicholson, J. FUS/ERG gene fusions in Ewing's tumors. Cancer Res 2003;63:4568–4576.Google ScholarPubMed
Ng, TL, O'Sullivan, MJ, Pallen, CJ, Hayes, M, Clarkson, PW, Winstanley, M. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn 2007;9:459–463.CrossRefGoogle Scholar
Sandberg, AA, Bridge, JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumor: Gastrointestinal stromal tumors. Cancer Genet Cytogenet 2002;135:1–22.CrossRefGoogle ScholarPubMed
López-Guerrero, JA, Noguera, R, Llombart-Bosch, A. GIST: particular aspects related to cell cultures, xenografts, and cytogenetics. Semin Diagn Pathol 2006;23:103–110.CrossRefGoogle ScholarPubMed
Wozniak, A, Sciot, R, Guillou, L, Pauwels, P, Wasag, B, Stul, M. Array CGH analysis in primary gastrointestinal stromal tumors: cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status. Genes Chromosomes Cancer 2007;46:261–276.CrossRefGoogle ScholarPubMed
Sandberg, AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma. Cancer Genet Cytogenet 2004;155:1–24.CrossRefGoogle ScholarPubMed
Meis-Kindblom, JM, Sjogren, H, Kindblom, LG, Peydro-Mellquist, A, Roijer, E, Aman, P. Cytogenetic and molecular genetic analyses of liposarcoma and its soft tissue simulators: recognition of new variants and differential diagnosis, Virchows Arch 2001;439:141–151.CrossRefGoogle ScholarPubMed
Segura-Sanchez, J, Gonzalez-Campora, R, Pareja-Megia, MJ, Garcia-Escudero, A, Galera-Ruiz, H, Lopez-Beltran, A. Chromosome-12 copy number alterations and MDM2, CDK4 and TP53 expression in soft tissue liposarcoma. Anticancer Res 2006;26:4937–4942.Google ScholarPubMed
Shimada, S, Ishizawa, T, Ishizawa, K, Matsumura, T, Hasegawa, T, Hirose, T. The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers. Hum Pathol 2006;37:1123–1129.CrossRefGoogle ScholarPubMed
Weaver, J, Downs-Kelly, E, Goldblum, JR, Turner, S, Kulkarni, S, Tubbs, RR. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol 2008;21:943–949.CrossRefGoogle ScholarPubMed
DeClue, JE, Papageorge, AG, Fletcher, JA, Diehl, SR, Ratner, N, Vass, WC. Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell 1992;69:265– 273.CrossRefGoogle Scholar
Knudson, AG. Mutation and statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820–823.CrossRefGoogle ScholarPubMed
Serra, E, Puig, S, Otero, D, Gaona, A, Kruyer, H, Ars, E. Confirmation of a double hit model for the NF1 gene in benign neurofibromas. Am J Hum Genet 1997;61:512–519.CrossRefGoogle ScholarPubMed
Storlazzi, CT, Steyern, FV, Domanski, HA, Mandahl, N, Mertens, F. Biallelic somatic inactivation of the NF1 gene through chromosomal translocations in a sporadic neurofibroma. Int J Cancer 2005;117:1055–1057.CrossRefGoogle Scholar
Birindelli, S, Perrone, F, Oggionni, M, Lavarino, C, Pasini, B, Vergani, B. Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors. Lab Invest 2001;81:833–844.CrossRefGoogle ScholarPubMed
Legius, E, Dierick, H, Wu, R, Hall, BK, Marynen, P, Cassiman, JJ. TP53 mutations are frequent in malignant NF1 tumors. Genes Chromosomes Cancer 1994;10:250–255.CrossRefGoogle ScholarPubMed
Kourea, HP, Orlow, I, Scheithauer, BW, Cordon-Cardo, C, Woodruff, JM. Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas. Am J Pathol 1999;155:1855–60.CrossRefGoogle ScholarPubMed
Berner, JM, Sorlie, T, Mertens, F, Henriksen, J, Saeter, G, Mandahl, N. Chromosome band 9p21 is frequently altered in malignant peripheral nerve sheath tumors: studies of CDKN2A and other genes of the pRB pathway. Genes Chromosomes Cancer 1999;26:151–160.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Nielsen, GP, Stemmer-Rachamimov, AO, Ino, Y, Moller, MB, Rosenberg, AE, Louis, DN. Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation. Am J Pathol 1999;155:1879–(1884).CrossRefGoogle ScholarPubMed
Perrone, F, Tabano, S, Colombo, F, Dagrada, G, Birindelli, S, Gronchi, A. p15INK4b, p14ARF, and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. Clin Cancer Res 2003;9:4132–4138.Google ScholarPubMed
Agesen, TH, Flørenes, VA, Molenaar, WM, Lind, GE, Berner, JM, Plaat, BE. Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. J Neuropathol Exp Neurol 2005;64:74–81.CrossRefGoogle ScholarPubMed
Carroll, SL, Stonecypher, MS. Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors: II. The role of dysregulated growth factor signaling. J Neuropathol Exp Neurol 2005;64:1–9.CrossRefGoogle ScholarPubMed
Schmidt, H, Wurl, P, Taubert, H, Meye, A, Bache, M, Holzhausen, HJ. Genomic imbalances of 7p and 17q in malignant peripheral nerve sheath tumors are clinically relevant. Genes Chromosomes Cancer 1999;25:205–211.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Skotheim, RI, Kallioniemi, A, Bjerkhagen, B, Mertens, F, Brekke, HR, Monni, O. Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors and associated with clinical outcome. J Clin Oncol 2003;21:4586–4591.CrossRefGoogle ScholarPubMed
Storlazzi, CT, Brekke, HR, Mandahl, N, Brosjö, O, Smeland, S, Lothe, RA. Identification of a novel amplicon at distal 17q containing the BIRC5/SURVIVIN gene in malignant peripheral nerve sheath tumours. J Pathol 2006;209:492–500.CrossRefGoogle ScholarPubMed
Kresse, SH, Skårn, M, Ohnstad, HO, Namløs, HM, Bjerkehagen, B, Myklebost, O. DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH. Mol Cancer 2008;7:48.CrossRefGoogle ScholarPubMed
Huang, HY, Illei, PB, Zhao, Z, Mazumdar, M, Healey, JH, Huvos, AG. Ewing sarcomas with p53 mutations or p16/p14ARF homozygous deletions: a highly aggressive subset associated with poor chemoresponse. J Clin Oncol 2005;23:548–558.CrossRefGoogle ScholarPubMed
Antonescu, CR, Tschernyavsky, SJ, Decuseara, R, Leung, DH, Woodruff, JM, Brennan, MF. Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 2001;7:3977–3987.Google ScholarPubMed
Drobnjak, M, Latres, E, Pollack, D, Karpeh, M, Dudas, M, Woodruff, JM. Prognostic implications of p53 nuclear overexpression and high proliferation index of Ki-67 in adult soft-tissue sarcomas. J Natl Cancer Inst 1994;86:549–554.CrossRefGoogle ScholarPubMed
Wurl, P, Taubert, H, Meye, A, Berger, D, Lautenschlager, C, Holzhausen, HJ. Prognostic value of immunohistochemistry for p53 in primary soft-tissue sarcomas: a multivariate analysis of five antibodies. J Cancer Res Clin Oncol 1997;123:502–508.CrossRefGoogle ScholarPubMed
Cordon-Cardo, C, Latres, E, Drobnjak, M, Oliva, MR, Pollack, D, Woodruff, JM. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res 1994;54:794–799.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×