title: Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.
abstract: BACKGROUND
  The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau (VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α (HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC).
  
  
  METHODS
  In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/-14q (VHL-WT plus HIF2α [WT/H2]), -3p/+14q (HIF1α and HIF2α [H1H2]), and -3p/-14q (HIF2α [H2]).
  
  
  RESULTS
  Among patients who had loss of 3p, tumors with -3p/-14q (H2) alterations were larger (P = .002), had higher grade (P = .002) and stage (P = .001), and more often were metastatic (P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with -3p/-14q (H2) had worse cancer-specific survival (P = .014), and patients who had localized disease (P = .012) and primary T1 (pT1) tumors (P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses.
  
  
  CONCLUSIONS
  Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC.
authors: Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA.
authors: Nils
authors: N
authors: Kroeger
authors: Tobias
authors: T
authors: Klatte
authors: Karim
authors: K
authors: Chamie
authors: P Nagesh
authors: PN
authors: Rao
authors: Frédéric D
authors: FD
authors: Birkhäuser
authors: Geoffrey A
authors: GA
authors: Sonn
authors: Joseph
authors: J
authors: Riss
authors: Fairooz F
authors: FF
authors: Kabbinavar
authors: Arie S
authors: AS
authors: Belldegrun
authors: Allan J
authors: AJ
authors: Pantuck
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D002893:Chromosomes, Human, Pair 3; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D016019:Survival Analysis; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human