Title | Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Xu, J, Reznik, E, Lee, H-J, Gundem, G, Jonsson, P, Sarungbam, J, Bialik, A, Sánchez-Vega, F, Creighton, CJ, Hoekstra, J, Zhang, L, Sajjakulnukit, P, Kremer, D, Tolstyka, Z, Casuscelli, J, Stirdivant, S, Tang, J, Schultz, N, Jeng, P, Dong, Y, Su, W, Cheng, EH, Russo, P, Coleman, JA, Papaemmanuil, E, Chen, Y-B, Reuter, VE, Sander, C, Kennedy, SR, Hsieh, JJ, Lyssiotis, CA, Tickoo, SK, A Hakimi, A |
Journal | Elife |
Volume | 8 |
Date Published | 2019 Apr 01 |
ISSN | 2050-084X |
Keywords | Aerobiosis, Carcinoma, Renal Cell, Cell Respiration, Histocytochemistry, Humans, Immunohistochemistry, Kidney Neoplasms, Metabolic Networks and Pathways, Oxidation-Reduction |
Abstract | 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. |
DOI | 10.7554/eLife.38986 |
Alternate Journal | Elife |
PubMed ID | 30924768 |
PubMed Central ID | PMC6459676 |
Grant List | Program in Chemical Biology - Graduate Assistance in Areas of National Need (GAANN) award / / University of Michigan / International Graduate Assistance in Areas of National Need (GAANN) award / / University of Michigan's Program in Chemical Biology / International P30 CA008748 / CA / NCI NIH HHS / United States Dale F. Frey Award for Breakthrough Scientists, DFS-09-14 / DRCRF / Damon Runyon Cancer Research Foundation / United States Junior Scholar Award, V2016-009 / / V Foundation for Cancer Research / International Research Scholar Award / / American Urological Association / International Kimmel Scholar Award SKF-16-005 / / Sidney Kimmel Foundation for Cancer Research / International Sidney Kimmel Center for Prostate and Urologic Cancers / / Sidney Kimmel Foundation for Cancer Research / International P30 CA046592 / CA / NCI NIH HHS / United States Kimmel Scholar Award, SKF-16-005 / / Sidney Kimmel Foundation for Cancer Research / International DK097153 / NH / NIH HHS / United States Junior Scholar Award V2016-009 / / V Foundation for Cancer Research / International Dale F. Frey Award for Breakthrough Scientists DFS-09-14 / DRCRF / Damon Runyon Cancer Research Foundation / United States |
Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma.
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