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.
Source: A
remarkably simple genome underlies highly malignant pediatric rhabdoid cancers.
Lee RS, Stewart C, Carter SL, Ambrogio L, Cibulskis K, Sougnez C, Lawrence MS,
Auclair D, Mora J, Golub TR, Biegel JA (biegel@mail.med.upenn.edu), Getz G
(gadgetz@broadinstitute.org),
Roberts CW (Charles_Roberts@dfci.harvard.edu).
J Clin Invest. 2012 Jul 16.
Free
paper available at:
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