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Zytogenetische Veränderungen bei Nierentumoren

Einsatzmöglichkeiten von Chromosomen-CGH und Fluoreszenz-in-situ-Hybridisierung

Cytogenetic alterations in renal tumors

Applications for comparative genomic hybridization and fluorescence in situ hybridization

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Zusammenfassung

Die WHO-Klassifikation der Nierenzellkarzinome (NZ-Ca) berücksichtigt chromosomale Veränderungen. Neuere zytogenetische Techniken wie komparative genomische Hybridisierung (CGH) und Fluoreszenz-in-situ-Hybridisierung (FISH) bieten Alternativen zur klassischen Zytogenetik. Bei klarzelligen NZ-Ca sind Verluste in 3p die häufigste Veränderung. Papilläre NZ-Ca sind durch Tri-/Tetrasomien und Verlust des Y-Chromosoms charakterisiert. CGH-Analysen zeigen, dass die Anzahl der DNA-Zugewinne bei papillären NZ-Ca des Typ I signifikant höher ist als bei Typ II. In chromophoben NZ-Ca dominieren DNA-Verluste der Chromosomen 1, 2, 6, 10, 13, 17 und 21. Onkozytome werden in eine Gruppe mit Rearrangements der Region 11q13 und eine mit Verlusten des Chromosoms 1 und der Geschlechtschromosomen unterteilt. Translokationen mit Beteiligung des Chromosoms 3, wie t(3;8)(p14.2;q24.13) und t(2;3)(q35;q21) sind bei familiären klarzelligen NZ-Ca beschrieben. Bei einigen männlichen Patienten mit tubulopapillären Nierentumoren ist die Translokation t(X;1)(p11.2;q21.2) beschrieben. Obwohl zur histopathologischen Nierentumordiagnostik meist keine Zusatzuntersuchungen nötig sind, können CGH und FISH die Diagnosestellung stützen und in einzelnen, sehr schwierigen Fällen eine definitive Diagnosefindung ermöglichen.

Abstract

The WHO classification of renal cell carcinomas (RCC) takes into account chromosomal alterations. New cytogenetic techniques such as comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) offer alternative methods to the classic cytogenetic banding technique. Clear cell (classic) RCC frequently show the loss of 3p. Papillary RCC are characterized by trisomies and tetrasomies as well as loss of the Y chromosome. CGH analysis demonstrates that DNA copy increase is more common in type I papillary RCC compared to type II. Chromophobe RCC are characterized by losses in chromosomes 1, 2, 6, 10, 13, 17, and 21. Oncocytomas can be divided into cases with rearrangements in the 11q13 region and those with loss of chromosome 1 and the sex chromosomes. Translocations involving chromosome 3, such as t(3;8)(p14;q24.13) and t(2;3)(q35;q21) have been described in familial clear cell RCC. The most recent class of RCC, seen only in men, is referred to as translocation tumors. These tumors demonstrate a tubulopapillary growth pattern and have a t(X;1)(p11.2;q21.2) translocation. Although not required for most clinical diagnoses, CGH and FISH complement the standard histologic diagnosis of RCC and may provide a definitive diagnosis in a small number of challenging cases.

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Literatur

  1. Argani P, Ladanyi M (2005) Translocation carcinomas of the kidney. Clin Lab Med 25: 363–78

    Article  PubMed  Google Scholar 

  2. Bauman JG, Wiegant J, Borst P, van Duijn P (1980) A new method for fluorescence microscopical localization of specific DNA sequences by in situ hybridization of fluorochromelabelled RNA. Exp Cell Res 128: 485–490

    Article  PubMed  Google Scholar 

  3. Bissig H, Richter J, Desper R et al. (1999) Evaluation of the clonal relationship between primary and metastatic renal cell carcinoma by comparative genomic hybridization. Am J Pathol 155: 267–274

    PubMed  Google Scholar 

  4. Bodmer D, Eleveld M, Kater-Baats E et al. (2002) Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). Hum Mol Genet 11: 641–649

    Article  PubMed  Google Scholar 

  5. Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG (2002) Understanding familial and non-familial renal cell cancer. Hum Mol Genet 11: 2489–2498

    Article  PubMed  Google Scholar 

  6. Brunelli M, Eble JN, Zhang S, Martignoni G, Cheng L (2003) Gains of chromosomes 7, 17, 12, 16, and 20 and loss of Y occur early in the evolution of papillary renal cell neoplasia: a fluorescent in situ hybridization study. Mod Pathol 16: 1053–1059

    Article  PubMed  Google Scholar 

  7. Corless CL, Aburatani H, Fletcher JA, Housman DE, Amin MB, Weinberg DS (1996) Papillary renal cell carcinoma: quantitation of chromosomes 7 and 17 by FISH, analysis of chromosome 3p for LOH, and DNA ploidy. Diagn Mol Pathol 5: 53–64

    Article  PubMed  Google Scholar 

  8. Fischer J, Palmedo G, von Knobloch R, Bugert P, Prayer-Galetti T, Pagano F, Kovacs G (1998) Duplication and overexpression of the mutant allele of the MET proto- oncogene in multiple hereditary papillary renal cell tumours. Oncogene 17: 733–739

    Article  PubMed  Google Scholar 

  9. Fuzesi L, Gunawan B, Braun S, Bergmann F, Brauers A, Effert P, Mittermayer C (1998) Cytogenetic analysis of 11 renal oncocytomas: further evidence of structural rearrangements of 11q13 as a characteristic chromosomal anomaly. Cancer Genet Cytogenet 107: 1–6

    Article  PubMed  Google Scholar 

  10. Garraway LA, Widlund HR, Rubin MA et al. (2005) Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436: 117–122

    Article  PubMed  Google Scholar 

  11. Gemmill RM, West JD, Boldog F et al. (1998) The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci USA 95: 9572–9577

    Article  PubMed  Google Scholar 

  12. Harrison CJ, Foroni L (2002) Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Rev Clin Exp Hematol 6: 91–113; discussion 200–112

    Article  PubMed  Google Scholar 

  13. Jiang F, Desper R, Papadimitriou CH et al. (2000) Construction of evolutionary tree models for renal cell carcinoma from comparative genomic hybridization data. Cancer Res 60: 6503–6509

    PubMed  Google Scholar 

  14. Jiang F, Richter J, Schraml P et al. (1998) Chromosomal imbalances in papillary renal cell carcinoma: Genetic differences between histologic subtypes. Am J Pathol 153: 1467–1473

    PubMed  Google Scholar 

  15. Kallioniemi A, Kallioniemi O, Sudar D, Rutovitz D, Gray J, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258: 818–821

    PubMed  Google Scholar 

  16. Knuutila S, Bjorkqvist AM, Autio K et al. (1998) DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol 152: 1107–1123

    PubMed  Google Scholar 

  17. Levsky JM, Singer RH (2003) Fluorescence in situ hybridization: past, present and future. J Cell Sci 116: 2833–2838

    Article  PubMed  Google Scholar 

  18. Moch H, Presti JC Jr, Sauter G, Buchholz N, Jordan P, Mihatsch MJ, Waldman FM (1996) Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma. Cancer Res 56: 27–30

    PubMed  Google Scholar 

  19. Presti J, Moch H, Reuter V, Huynh D, Waldman F (1996) Chromosome 1 and 14 loss in renal oncocytomas. Genes Chromos Cancer 17: 199–204

    Article  PubMed  Google Scholar 

  20. Receveur AO, Couturier J, Molinie V et al. (2005) Characterization of quantitative chromosomal abnormalities in renal cell carcinomas by interphase four-color fluorescence in situ hybridization. Cancer Genet Cytogenet 158: 110–118

    Article  PubMed  Google Scholar 

  21. Reutzel D, Mende M, Naumann S, Storkel S, Brenner W, Zabel B, Decker J (2001) Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization. Cytogenet Cell Genet 93: 221–227

    Article  PubMed  Google Scholar 

  22. Sanjmyatav J, Rubtsov N, Starke H, Schubert J, Hindermann W, Junker K (2005) Identification of tumor entities of renal cell carcinoma using interphase fluorescence in situ hybridization. J Urol 174: 731–735

    Article  PubMed  Google Scholar 

  23. Schullerus D, von Knobloch R, Chudek J, Herbers J, Kovacs G (1999) Microsatellite analysis reveals deletion of a large region at chromosome 8p in conventional renal cell carcinoma. Int J Cancer 80: 22–24

    Article  PubMed  Google Scholar 

  24. Sidhar SK, Clark J, Gill S et al. (1996) The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet 5: 1333–1338

    Article  PubMed  Google Scholar 

  25. Speicher M, Schoell B, Du Manoir S et al. (1994) Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol 145: 356–364

    PubMed  Google Scholar 

  26. Swiger RR, Tucker JD (1996) Fluorescence in situ hybridization: a brief review. Environ Mol Mutagen 27: 245–254

    Article  PubMed  Google Scholar 

  27. van Kessel AG, Wijnhoven H, Bodmer D et al. (1999) Renal cell cancer: chromosome 3 translocations as risk factors. J Natl Cancer Inst 91: 1159–1160

    Article  PubMed  Google Scholar 

  28. Weiss MM, Hermsen MA, Meijer GA et al. (1999) Comparative genomic hybridisation. Mol Pathol 52: 243–251

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    K. D. Mertz, J. Tchinda, M. A. Rubin &  S. Perner

  2. Harvard Medical School, Boston, MA, USA

    K. D. Mertz, J. Tchinda, M. A. Rubin &  S. Perner

  3. Dana-Farber Cancer Institute, Boston, MA, USA

    M. A. Rubin

  4. Abteilung Urologie, Universitätsklinikum Ulm

    R. Küfer

  5. Institut für Pathologie, Universitätsklinikum Ulm

    P. Möller &  S. Perner

  6. Institut für Klinische Pathologie, Universitätsspital Zürich

    K. D. Mertz & H. Moch

  7. Department of Pathology, Brigham and Women’s Hospital, 221 Longwood Ave, EBRC #420, Boston, MA 02115, USA

    S. Perner

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  1. K. D. Mertz
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  2. J. Tchinda
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Correspondence to S. Perner.

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Mertz, K.D., Tchinda, J., Küfer, R. et al. Zytogenetische Veränderungen bei Nierentumoren. Urologe 45, 316–322 (2006). https://doi.org/10.1007/s00120-006-1004-z

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  • DOI: https://doi.org/10.1007/s00120-006-1004-z

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