Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests aberrant chromatin regulation as a crucial step in ccRCC development

被引：68

作者：

Duns, Gerben ^{[1
]}

Hofstra, Robert M. W. ^{[1
]}

Sietzema, Jantine G. ^{[1
]}

Hollema, Harry ^{[2
]}

van Duivenbode, Inge ^{[1
]}

Kuik, Angela ^{[1
]}

Giezen, Cor ^{[1
]}

Osinga, Jan ^{[1
]}

Bergsma, Jelkje J. ^{[1
]}

Bijnen, Harrie ^{[1
]}

van der Vlies, Pieter ^{[1
]}

van den Berg, Eva ^{[1
]}

Kok, Klaas ^{[1
]}

机构：

[1] Univ Groningen, Dept Genet, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands

[2] Univ Groningen, Dept Pathol & Med Biol, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands

来源：

HUMAN MUTATION | 2012年 / 33卷 / 07期

关键词：

ccRCC; chromosome; 3; tumor suppressor; SETD2; PBRM1; BAP1; chromatin remodeling; VHL; SENESCENCE; INDUCTION; COMPLEX; BAF180; CANCER;

D O I：

10.1002/humu.22090

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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. Hum Mutat 33:10591062, 2012. (c) 2012 Wiley Periodicals, Inc.

引用

页码：1059 / 1062

页数：4

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