Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies

Kimryn W. Rathmell4,5,6, Fengju Chen1 and Chad J. Creighton1,2,3

1 The Dan L. Duncan Cancer Center Division of Biostatistics, Houston, TX, USA

2 Department of Medicine, Baylor College of Medicine, Houston, TX, USA

3 Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

4 Department of Urology, University of North Carolina, Chapel Hill, NC

5 Department of Genetics, University of North Carolina, Chapel Hill, NC

6 Department of Medicine, Division of Hematology and Oncology, University of North Carolina, Chapel Hill, NC


Chad J. Creighton, email:

Keywords: ChRCC, chromophobe, kidney cancer, genomics, TERT, TCGA, mitochondria

Received: January 27, 2015 Accepted: February 18, 2015 Published: February 20, 2015


Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell carcinomas, a heterogenous group of cancers arising from the nephron. Recently, The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple data platforms, including whole exome sequencing, whole genome sequencing (WGS), and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study would have implications for other types of kidney cancer as well as for cancer biology in general. Global molecular patterns in ChRCC provided clues as to this cancer’s cell of origin, which is distinct from that of the other renal cell carcinomas, illustrating an approach that might be applied towards elucidating the cell of origin of other cancer types. MtDNA sequencing revealed loss-of-function mutations in NADH dehydrogenase subunits, highlighting the role of deregulated metabolism in this and other cancers. Analysis of WGS data led to the discovery of recurrent genomic rearrangements involving TERT promoter region, which were associated with very high expression levels of TERT, pointing to a potential mechanism for TERT deregulation that might be found in other cancers. WGS data, generated by large scale efforts such as TCGA and the International Cancer Genomics Consortium (ICGC), could be more extensively mined across various cancer types, to uncover structural variants, mtDNA mutations, themes of tumor metabolic properties, as well as noncoding point mutations. TCGA’s data on ChRCC should continue to serve as a resource for future pan-cancer as well as kidney cancer studies, and highlight the value of investigations into rare tumor types to globally inform principals of cancer biology.

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