title: Identification of genomic alterations associated with metastasis and cancer specific survival in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  We identified regions of DNA copy number changes that are significantly associated with metastasis and clinical outcome in patients with clear cell renal cell carcinoma.
  
  
  METHODS
  We analyzed 53 primary clear cell renal cell carcinomas, including 31 metastasized and 22 nonmetastasized tumors, by array comparative genomic hybridization with a median resolution of 1 to 1.5 Mbp. To validate copy number aberrations with potential prognostic value we performed fluorescence in situ hybridization analysis using commercially available fluorescent probes.
  
  
  RESULTS
  We identified 5 recurrent chromosomal aberrations that were significantly associated with metastasis, including gains of 1q21.3, 12q13.12, 12q13.3q14.1 and 20q11.21q13.2, and loss of 9p21.3p24.1. The most prominent of them with the highest OR for metastatic risk were loss of 9p21.3p24.1, and gains of 1q21.3 and 20q11.21q13.32. Eight alterations involving chromosomes 7, 9, 12, 16 and 20 significantly correlated with shortened cancer specific survival. The lowest p values on Kaplan-Meier analysis showed losses of 9p21.3p24.1 and 9q32q33.1, and gains of 7q36.3 and 20q11.21q13.32. Fluorescence in situ hybridization done in the same cohort for the 4 select regions 1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32 clearly confirmed the results of array comparative genomic hybridization.
  
  
  CONCLUSIONS
  Data suggest that specific chromosomal alterations in clear cell renal cell carcinoma can be used to predict metastasis and cancer specific survival in patients with clear cell renal cell carcinoma. It seems possible to design a combined fluorescence in situ hybridization assay based on these genetic targets for outcome prediction, which can be used for routine diagnostics.
authors.affiliation: Department of Urology and Pathology, Jena University Hospital, Jena, Germany. jimsgene.sanjmyatav@med.uni-jena.de
authors.forename: Jimsgene
authors.initials: J
authors.lastname: Sanjmyatav
authors.forename: Kerstin
authors.initials: K
authors.lastname: Junker
authors.forename: Sophie
authors.initials: S
authors.lastname: Matthes
authors.forename: Martin
authors.initials: M
authors.lastname: Muehr
authors.forename: Doriana
authors.initials: D
authors.lastname: Sava
authors.forename: Maria
authors.initials: M
authors.lastname: Sternal
authors.forename: Sven
authors.initials: S
authors.lastname: Wessendorf
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Heiko
authors.initials: H
authors.lastname: Wunderlich
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwaenen
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis