Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma
© 2019, Xu et al..
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.
| Errataetall: |
CommentIn: Nat Rev Nephrol. 2019 Jul;15(7):388. - PMID 30988522 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
eLife - 8(2019) vom: 01. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Jianing [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer biology |
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| Anmerkungen: |
Date Completed 30.03.2020 Date Revised 21.05.2021 published: Electronic CommentIn: Nat Rev Nephrol. 2019 Jul;15(7):388. - PMID 30988522 Citation Status MEDLINE |
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| doi: |
10.7554/eLife.38986 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma |
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| 500 | |a CommentIn: Nat Rev Nephrol. 2019 Jul;15(7):388. - PMID 30988522 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019, Xu et al. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a genetics | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a human | |
| 650 | 4 | |a kidney cancer | |
| 650 | 4 | |a metabolomics | |
| 650 | 4 | |a mitochondrial DNA | |
| 650 | 4 | |a sorbitol | |
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