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题目:: The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to Tumorigenesis.
作者:: Joshi(Shilpy),Tolkunov(Denis),Aviv(Hana),Hakimi(Abraham A),Yao(Ming),Hsieh(James J),Ganesan(Shridar),Chan(Chang S),White(Eileen)
状态:: 发布时间2015-12-15 , 更新时间 2016-10-19
期刊:: Cell Rep
摘要:: 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.
语言:: eng
DOI:

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