TY - JOUR
T1 - Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma
AU - Xu, Jianing
AU - Reznik, Ed
AU - Lee, Ho Joon
AU - Gundem, Gunes
AU - Jonsson, Philip
AU - Sarungbam, Judy
AU - Bialik, Anna
AU - Sanchez-Vega, Francisco
AU - Creighton, Chad J.
AU - Hoekstra, Jake
AU - Zhang, Li
AU - Sajjakulnukit, Peter
AU - Kremer, Daniel
AU - Tolstyka, Zachary
AU - Casuscelli, Jozefina
AU - Stirdivant, Steve
AU - Tang, Jie
AU - Schultz, Nikolaus
AU - Jeng, Paul
AU - Dong, Yiyu
AU - Su, Wenjing
AU - Cheng, Emily H.
AU - Russo, Paul
AU - Coleman, Jonathan A.
AU - Papaemmanui, Elli
AU - Chen, Ying Bei
AU - Reuter, Victor E.
AU - Sander, Chris
AU - Kennedy, Scott R.
AU - Hsieh, James J.
AU - Lyssiotis, Costas A.
AU - Tickoo, Satish K.
AU - Ari Hakimi, A.
N1 - Funding Information:
Damon Runyon Cancer Research Foundation Dale F. Frey Award for Breakthrough Scientists, DFS-09-14 Costas A Lyssiotis. V Foundation for Cancer Research Junior Scholar Award, V2016-009 Costas A Lyssiotis Sidney Kimmel Foundation for Cancer Research Kimmel Scholar Award, SKF16-005 Costas A Lyssiotis National Institutes of Health DK097153 Costas A Lyssiotis Charles Woodson Research Fund Costas A Lyssiotis The UM Pediatric Brain Tumor Initiative Costas A Lyssiotis University of Michigan Program in Chemical Biology Graduate Assistance in Areas of National Need (GAANN) award Daniel Kremer National Cancer Institute P30 CA008748 Jianing Xu Ed Reznik Gunes Gundem Philip Jonsson Judy Sarungbam Anna Bialik Francisco Sanchez-Vega Jozefina Casuscelli Nikolaus Schultz Yiyu Dong Paul Russo Jonathan A Coleman Elli Papaemmanuil Ying-Bei Chen Victor E Reuter Chris Sander Satish K Tickoo A Ari Hakimi National Cancer Institute P30 CA046592 Costas A Lyssiotis Sidney Kimmel Foundation for Cancer Research A Ari Hakimi American Urological Association Research Scholar Award A Ari Hakimi.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.38986
DO - 10.7554/eLife.38986
M3 - Article
C2 - 30924768
AN - SCOPUS:85064573309
VL - 8
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e38986
ER -