TY  - JOUR
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
Y1  - 2012/11/02 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.141382.112 
SP  - gr.141382.112 
UR  - http://genome.cshlp.org/content/early/2012/11/01/gr.141382.112.abstract 
N2  - 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. 
ER  -