RT Journal
A1 Drier, Yotam
A1 Lawrence, Michael S
A1 Carter, Scott L
A1 Stewart, Chip
A1 Gabriel, Stacey B
A1 Lander, Eric S
A1 Meyerson, Matthew
A1 Beroukhim, Rameen
A1 Getz, Gad
T1 Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability
JF Genome Research 
JO Genome Research 
YR 2012 
FD November 02 
DO 10.1101/gr.141382.112 
SP gr.141382.112 
UL http://genome.cshlp.org/content/early/2012/11/01/gr.141382.112.abstract 
AB Whole genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to basepair resolution allows analysis of rearrangement microhomology and genomic location for every sample. Here we analyze 95 tumor genome sequences from breast, head and neck, colorectal, and prostate carcinomas and from melanoma, multiple myeloma and chronic lymphocytic leukemia. We discover three genomic factors that are significantly correlated with the distribution of rearrangements: replication time, transcription rate and GC content. The correlation is complex and different patterns are observed between tumor types, within tumor types, and even between different types of rearrangements. Mutations in the APC gene correlate with, and hence potentially contribute to, DNA breakage in late replicating, low %GC, untranscribed regions of the genome. We show that somatic rearrangements display less microhomology than germline rearrangements, and that breakpoint loci are correlated with local hypermutability with a particular enrichment for C>G transversions.