The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis
Open accessAbstract
Oncocytomas are predominantly benign neoplasms possessing pathogenic mitochondrial mutations and accumulation of respiration-defective mitochondria, characteristics of unknown significance. Using exome and transcriptome sequencing, we identified two main subtypes of renal oncocytoma. Type 1 is diploid with CCND1 rearrangements, whereas type 2 is aneuploid with recurrent loss of chromosome 1, X or Y, and/or 14 and 21, which may proceed to more aggressive eosinophilic chromophobe renal cell carcinoma (ChRCC). Oncocytomas activate 5' adenosine monophosphate-activated protein kinase (AMPK) and Tp53 (p53) and display disruption of Golgi and autophagy/lysosome trafficking, events attributed to defective mitochondrial function. This suggests that the genetic defects in mitochondria activate a metabolic checkpoint, producing autophagy impairment and mitochondrial accumulation that limit tumor progression, revealing a novel tumor-suppressive mechanism for mitochondrial inhibition with metformin. Alleviation of this metabolic checkpoint in type 2 by p53 mutations may allow progression to eosinophilic ChRCC, indicating that they represent higher risk.
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Metadata
- Authors
- Joshi, S., Tolkunov, D., Aviv, H., Hakimi, A. A., Yao, M., Hsieh, J. J., Ganesan, S., Chan, C. S., & White, E.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 13
- Issue
- 9
- Pages
- 1895-1908
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2207569459
- Cited by
- 161
- References
- 8
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- gold
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- Joshi, S., Tolkunov, D., Aviv, H., Hakimi, A. A., Yao, M., Hsieh, J. J., Ganesan, S., Chan, C. S., & White, E. (2015). The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis. Cell Reports. https://doi.org/10.1016/j.celrep.2015.10.059
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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