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J Clin Invest DOI:10.1172/JCI64400

A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers.

Publication TypeJournal Article
Year of Publication2012
AuthorsLee, RS, Stewart, C, Carter, SL, Ambrogio, L, Cibulskis, K, Sougnez, C, Lawrence, MS, Auclair, D, Mora, J, Golub, TR, Biegel, JA, Getz, G, Roberts, CWM
JournalJ Clin Invest
Date Published2012 Aug
KeywordsChild, Preschool, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, DNA Mutational Analysis, DNA, Neoplasm, DNA-Binding Proteins, Exome, Female, Humans, Infant, Male, Mutation, Neoplasm Recurrence, Local, Polymorphism, Single Nucleotide, Rhabdoid Tumor, SMARCB1 Protein, Transcription Factors

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.


Alternate JournalJ. Clin. Invest.
PubMed ID22797305
PubMed Central IDPMC3408754
Grant ListU01 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