The somatic genomic landscape of chromophobe renal cell carcinoma

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticlepeer-review

619 Scopus citations

Abstract

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.

Original languageEnglish
Pages (from-to)319-330
Number of pages12
JournalCancer Cell
Volume26
Issue number3
DOIs
StatePublished - 2014

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