The somatic genomic landscape of chromophobe renal cell carcinoma

Cancer Cell. 2014 Sep 8;26(3):319-330. doi: 10.1016/j.ccr.2014.07.014. Epub 2014 Aug 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Renal Cell / genetics*
  • Chromosome Breakpoints
  • Chromosome Deletion
  • Chromosomes, Human / genetics
  • DNA Copy Number Variations
  • DNA Methylation
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Exome
  • Genome, Human
  • Humans
  • Kidney Neoplasms / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Telomerase / genetics
  • Transcriptome


  • DNA, Mitochondrial
  • TERT protein, human
  • Telomerase