A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers

被引：319

作者：

Lee, Ryan S. ^{[2
,3
]}

Stewart, Chip ^{[4
]}

Carter, Scott L. ^{[4
]}

Ambrogio, Lauren ^{[4
]}

Cibulskis, Kristian ^{[4
]}

Sougnez, Carrie ^{[4
]}

Lawrence, Michael S. ^{[4
]}

Auclair, Daniel ^{[4
]}

Mora, Jaume ^{[5
]}

Golub, Todd R. ^{[2
,3
,4
,6
]}

Biegel, Jaclyn A. ^{[1
,7
]}

Getz, Gad ^{[4
]}

Roberts, Charles W. M. ^{[2
,3
,8
]}

机构：

[1] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Broad Inst, Cambridge, MA 02142 USA

[5] Hosp St Joan de Deu, Dept Pediat Oncol, Barcelona, Spain

[6] Howard Hughes Med Inst, Chevy Chase, MD USA

[7] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[8] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2012年 / 122卷 / 08期

关键词：

MUTATIONS; TUMOR; TUMORIGENESIS; SMARCB1/INI1; ARID1A;

D O I：

10.1172/JCI64400

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Cancer is principally considered a genetic disease, and numerous mutations are thought essential to drive its growth. However, the existence of genomically stable cancers and the emergence of mutations in genes that encode chromatin remodelers raise the possibility that perturbation of chromatin structure and epigenetic regulation are capable of driving cancer formation. Here we sequenced the exomes of 35 rhabdoid tumors, highly aggressive cancers of early childhood characterized by biallelic loss of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. We identified an extremely low rate of mutation, with loss of SMARCB1 being essentially the sole recurrent event. Indeed, in 2 of the cancers there were no other identified mutations. Our results demonstrate that high mutation rates are dispensable for the genesis of cancers driven by mutation of a chromatin remodeling complex. Consequently, cancer can be a remarkably genetically simple disease.

引用

页码：2983 / 2988

页数：6

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