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

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

Authors:	Xu, J.; Reznik, E.; Lee, H. J.; Gundem, G.; Jonsson, P.; Sarungbam, J.; Bialik, A.; Sanchez-Vega, F.; Creighton, C. J.; 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, E. H.; Russo, P.; Coleman, J. A.; Papaemmanuil, E.; Chen, Y. B.; Reuter, V. E.; Sander, C.; Kennedy, S. R.; Hsieh, J. J.; Lyssiotis, C. A.; Tickoo, S. K.; Hakimi, A. A.
Article Title:	Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma
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.
Keywords:	gene; tumor; mutations; degradation; landscape; metabolomics; distinct; emphasis; mitochondrial-dna; set enrichment analysis
Journal Title:	eLife
Volume:	8
ISSN:	2050-084X
Publisher:	eLife Sciences Publications Ltd.
Date Published:	2019-04-01
Start Page:	e38986
Language:	English
ACCESSION:	WOS:000464311600001
DOI:	10.7554/eLife.38986
PROVIDER:	wos
PMCID:	PMC6459676
PUBMED:	30924768
Notes:	Article -- e38986 -- Source: Wos