Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma

oleh: Jianing Xu, Ed Reznik, Ho-Joon Lee, Gunes Gundem, Philip Jonsson, Judy Sarungbam, Anna Bialik, Francisco Sanchez-Vega, Chad J Creighton, Jake Hoekstra, Li Zhang, Peter Sajjakulnukit, Daniel Kremer, Zachary Tolstyka, Jozefina Casuscelli, Steve Stirdivant, Jie Tang, Nikolaus Schultz, Paul Jeng, Yiyu Dong, Wenjing Su, Emily H Cheng, Paul Russo, Jonathan A Coleman, Elli Papaemmanuil, Ying-Bei Chen, Victor E Reuter, Chris Sander, Scott R Kennedy, James J Hsieh, Costas A Lyssiotis, Satish K Tickoo, A Ari Hakimi

Format: Article
Diterbitkan: eLife Sciences Publications Ltd 2019-03-01

Deskripsi

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.