• Steffen Durinck, Eric W Stawiski, Andrea Pavía-Jiménez, Zora Modrusan, Payal Kapur, Bijay S Jaiswal, Na Zhang, Vanina Toffessi-Tcheuyap, Thong T Nguyen, Kanika Bajaj Pahuja, Ying-Jiun Chen, Sadia Saleem, Subhra Chaudhuri, Sherry Heldens, Marlena Jackson, Samuel Peña-Llopis, Joseph Guillory, Karen Toy, Connie Ha, Corissa J Harris, Eboni Holloman, Haley M Hill, Jeremy Stinson, Celina Sanchez Rivers, Vasantharajan Janakiraman, Weiru Wang, Lisa N Kinch, Nick V Grishin, Peter M Haverty, Bernard Chow, Julian S Gehring, Jens Reeder, Gregoire Pau, Thomas D Wu, Vitaly Margulis, Yair Lotan, Arthur Sagalowsky, Ivan Pedrosa, Frederic J de Sauvage, James Brugarolas, and Somasekar Seshagiri.
• Molecular Biology Department, Genentech, Inc., South San Francisco, California, USA.
• Nat. Genet. 2015 Jan 1; 47 (1): 13-21.

AbstractTo further understand the molecular distinctions between kidney cancer subtypes, we analyzed exome, transcriptome and copy number alteration data from 167 primary human tumors that included renal oncocytomas and non-clear cell renal cell carcinomas (nccRCCs), consisting of papillary (pRCC), chromophobe (chRCC) and translocation (tRCC) subtypes. We identified ten significantly mutated genes in pRCC, including MET, NF2, SLC5A3, PNKD and CPQ. MET mutations occurred in 15% (10/65) of pRCC samples and included previously unreported recurrent activating mutations. In chRCC, we found TP53, PTEN, FAAH2, PDHB, PDXDC1 and ZNF765 to be significantly mutated. Gene expression analysis identified a five-gene set that enabled the molecular classification of chRCC, renal oncocytoma and pRCC. Using RNA sequencing, we identified previously unreported gene fusions, including ACTG1-MITF fusion. Ectopic expression of the ACTG1-MITF fusion led to cellular transformation and induced the expression of downstream target genes. Finally, we observed upregulation of the anti-apoptotic factor BIRC7 in MiTF-high RCC tumors, suggesting a potential therapeutic role for BIRC7 inhibitors.

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