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- Title
Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.
- Authors
Kroeger, Nils; Klatte, Tobias; Chamie, Karim; Rao, P. Nagesh; Birkhäuser, Frédéric D.; Sonn, Geoffrey A.; Riss, Joseph; Kabbinavar, Fairooz F.; Belldegrun, Arie S.; Pantuck, Allan J.
- 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. Cancer 2013. © 2013 American Cancer Society.
- Subjects
RENAL cell carcinoma; CHROMOSOMES; TUMOR suppressor genes; CANCER; TUMORS
- Publication
Cancer (0008543X), 2013, Vol 119, Issue 8, p1547
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.27947