A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers.
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.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ryan S
RS
Lee
Chip
C
Stewart
Scott L
SL
Carter
Lauren
L
Ambrogio
Kristian
K
Cibulskis
Carrie
C
Sougnez
Michael S
MS
Lawrence
Daniel
D
Auclair
Jaume
J
Mora
Todd R
TR
Golub
Jaclyn A
JA
Biegel
Gad
G
Getz
Charles W M
CW
Roberts
D002675:Child, Preschool; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors