%0 Journal Article %J Elife %D 2019 %T Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. %A Xu, Jianing %A Reznik, Ed %A Lee, Ho-Joon %A Gundem, Gunes %A Jonsson, Philip %A Sarungbam, Judy %A Bialik, Anna %A Sánchez-Vega, Francisco %A Creighton, Chad J %A Hoekstra, Jake %A Zhang, Li %A Sajjakulnukit, Peter %A Kremer, Daniel %A Tolstyka, Zachary %A Casuscelli, Jozefina %A Stirdivant, Steve %A Tang, Jie %A Schultz, Nikolaus %A Jeng, Paul %A Dong, Yiyu %A Su, Wenjing %A Cheng, Emily H %A Russo, Paul %A Coleman, Jonathan A %A Papaemmanuil, Elli %A Chen, Ying-Bei %A Reuter, Victor E %A Sander, Chris %A Kennedy, Scott R %A Hsieh, James J %A Lyssiotis, Costas A %A Tickoo, Satish K %A Hakimi, A Ari %K Aerobiosis %K Carcinoma, Renal Cell %K Cell Respiration %K Histocytochemistry %K Humans %K Immunohistochemistry %K Kidney Neoplasms %K Metabolic Networks and Pathways %K Oxidation-Reduction %X

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver.

%B Elife %V 8 %8 2019 Apr 01 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/30924768?dopt=Abstract %R 10.7554/eLife.38986