Working with a team led by Seishi Ogawa from Kyoto University, we successfully elucidated a molecular landscape of clear-cell renal cell carcinoma (ccRCC). Using 240 specimens of ccRCC, we performed a multifaceted study including whole genomes or exomes, RNA sequences, DNA methylation and SNP array-based copy number analysis. We clarified the associations between the clinical outcome and mutation of VHL, PBRM1, BAP1 and SETD2, which are located at chr 3p, and further reported a newly identified mutation of TCEB1, which is involved in inactivation of VHL complexes. In addition, DNA methylation profiling revealed the high methylation clusters, which was also characterized by a higher BAP1 mutation rate and lower BAP1 and higher EZH2 expression levels by the integrative analyses, indicating that the cluster with high methylation was closely related to deregulated PRC2 activity. These comprehensive analyses of molecular profiling will open the avenue to improve the therapeutic efficacy and novel discovery of druggable targets and pathways against the intractable cancer.
These results are reported in the Nature Genetics, online publication.
Sato Y, Yoshizato T, Shiraishi Y, Maekawa S, Okuno Y, Kamura T, Shimamura T, Sato-Otsubo A, Nagae G, Suzuki H, Nagata Y, Yoshida K, Kon A, Suzuki Y, Chiba K, Tanaka H, Niida A, Fujimoto A, Tsunoda T, Morikawa T, Maeda D, Kume H, Sugano S, Fukayama M, Aburatani H, Sanada M, Miyano S, Homma Y, Ogawa S. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet. 2013 Jun 24. doi: 10.1038/ng.2699. [Epub ahead of print]
PMID: 23797736 [PubMed – as supplied by publisher]
