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Cancer Discov. 2011 Aug;1(3):222-35. doi: 10.1158/2159-8290.CD-11-0098. Epub 2011 Jun 7.

Genetic and functional studies implicate HIF1α as a 14q kidney cancer suppressor gene.

Author information

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Abstract

Kidney cancers often delete chromosome 3p, spanning the VHL tumor suppressor gene, and chromosome 14q, which presumably harbors ≥ 1 tumor suppressor genes. pVHL inhibits the hypoxia-inducible transcription factor (HIF), and HIF2α is a kidney cancer oncoprotein. In this article, we identify focal, homozygous deletions of the HIF1α locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1α suppresses renal carcinoma growth, but the products of these altered loci do not. Conversely, downregulation of HIF1α in HIF1α-proficient lines promotes tumor growth. HIF1α activity is diminished in 14q-deleted kidney cancers, and all somatic HIF1α mutations identified in kidney cancers tested to date are loss of function. Therefore, HIF1α has the credentials of a kidney cancer suppressor gene.

SIGNIFICANCE:

Deletion of 14q is a frequent event in clear cell renal carcinoma and portends a poor prognosis. In this study, we provide genetic and functional evidence that HIF1α is a target of 14q loss in kidney cancer.

KEYWORDS:

14q deletion, HIF1α, hypoxia, kidney cancer, tumor suppression, von Hippel-Lindau

Comment in

PMID:
22037472
[PubMed - indexed for MEDLINE]
PMCID:
PMC3202343
Free PMC Article

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