Clear cell renal cell carcinomas are characterized by 3p loss, and by inactivation of Von Hippel Lindau (VHL), a tumorsuppressor gene located at 3p25.
Recently, SETD2, located at 3p21, was identified as a new candidate ccRCC tumor-suppressor gene. The combined mutational frequency in ccRCC tumors of VHL and SETD2 suggests that there are still undiscovered tumor-suppressor genes on 3p. We screened all genes on 3p for mutations in 10 primary ccRCC tumors using exome-sequencing. We identified inactivating mutations in VHL, PBRM1, and BAP1. Sequencing of PBRM1 in ccRCC-derived cell lines confirmed its frequent inactivation in ccRCC. PBRM1 encodes for BAF180, the chromatin targeting subunit of the SWI/SNF complex. BAP1 encodes for BRCA1 associated protein-1, involved in histone deubiquitination. Taken together, the accumulating data suggest an important role for aberrant chromatin regulation in ccRCC development.
Written by:
Duns G, Hofstra RM, Sietzema JG, Hollema H, van Duivenbode I, Kuik A, Giezen C, Jan O, Bergsma JJ, Bijnen H, van der Vlies P, van den Berg E, Kok K. Are you the author?
Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
Reference: Hum Mutat. 2012 Jul;33(7):1059-62.
doi: 10.1002/humu.22090
PubMed Abstract
PMID: 22461374
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