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Re: The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis
- Source :
- Cell reports
- Publication Year :
- 2017
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2017.
-
Abstract
- SUMMARY 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.<br />Graphical abstract
- Subjects :
- business.industry
Urology
030232 urology & nephrology
Genomics
medicine.disease_cause
Bioinformatics
medicine.disease
Kidney Neoplasms
Article
Diagnosis, Differential
03 medical and health sciences
Cell Transformation, Neoplastic
0302 clinical medicine
medicine
Adenoma, Oxyphilic
Humans
Differential diagnosis
Carcinogenesis
business
Renal oncocytoma
Carcinoma, Renal Cell
Subjects
Details
- ISSN :
- 15273792 and 00225347
- Volume :
- 198
- Database :
- OpenAIRE
- Journal :
- Journal of Urology
- Accession number :
- edsair.doi.dedup.....b6300fbce63db749c9f5f4b22bc91ef4