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Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma
- Source :
- eLife, Vol 8 (2019)
- Publication Year :
- 2019
- Publisher :
- eLife Sciences Publications Ltd, 2019.
-
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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.6a397e8b7d454269bfb746b823085605
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.38986