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Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma
Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma CANCER Kroeger, N., Klatte, T., Chamie, K., Rao, P. N., Birkhaeuser, F. D., Sonn, G. A., Riss, J., Kabbinavar, F. F., Belldegrun, A. S., Pantuck, A. J. 2013; 119 (8): 1547-1554Abstract
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 1a (HIF-1a) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1a gene) in clear cell renal cell carcinoma (ccRCC).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 HIF2a [WT/H2]), -3p/+14q (HIF1a and HIF2a [H1H2]), and -3p/-14q (HIF2a [H2]).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.Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1a gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1a functions as an important tumor suppressor gene in ccRCC.
View details for DOI 10.1002/cncr.27947
View details for Web of Science ID 000317618700014