A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers.

J Clin Invest
Authors
Keywords
Abstract

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.

Year of Publication
2012
Journal
J Clin Invest
Volume
122
Issue
8
Pages
2983-8
Date Published
2012 Aug
ISSN
1558-8238
URL
DOI
10.1172/JCI64400
PubMed ID
22797305
PubMed Central ID
PMC3408754
Links
Grant list
U01 CA105423 / CA / NCI NIH HHS / United States
R01 CA046274 / CA / NCI NIH HHS / United States
R01 CA113794 / CA / NCI NIH HHS / United States
R01CA46274 / CA / NCI NIH HHS / United States
U01-1156106 / PHS HHS / United States
R01CA113794 / CA / NCI NIH HHS / United States