Journal
NATURE GENETICS
Volume 45, Issue 8, Pages 860-U191Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2699
Keywords
-
Categories
Funding
- KAKENHI [22134006]
- New Energy and Industrial Technology Development Organization (NEDO) [08C46598a]
- Japan Society for the Promotion of Science
- Council for Science and Technology Policy
- Grants-in-Aid for Scientific Research [24112006, 22134008, 25730173, 25670446, 22134006, 24700272] Funding Source: KAKEN
Ask authors/readers for more resources
Clear-cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer and its molecular pathogenesis is incompletely understood. Here we report an integrated molecular study of ccRCC in which >= 100 ccRCC cases were fully analyzed by whole-genome and/or whole-exome and RNA sequencing as well as by array-based gene expression, copy number and/or methylation analyses. We identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures and determined their impact on tumor behavior. Defective VHL-mediated proteolysis was a common feature of ccRCC, which was caused not only by VHL inactivation but also by new hotspot TCEB1 mutations, which abolished Elongin C-VHL binding, leading to HIF accumulation. Other newly identified pathways and components recurrently mutated in ccRCC included PI3K-AKT-mTOR signaling, the KEAP1-NRF2-CUL3 apparatus, DNA methylation, p53-related pathways and mRNA processing. This integrated molecular analysis unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available