Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability
Whole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair resolution allows analysis of rearrangement microhomology and genomic location for every sample...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2013
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| Online Access: | http://hdl.handle.net/1721.1/80787 |
| _version_ | 1826191898395541504 |
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| author | Drier, Yotam Lawrence, Michael S. Carter, Scott L. Stewart, Chip Gabriel, Stacey B. Meyerson, Matthew L. Beroukhim, Rameen Getz, Gad Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Drier, Yotam Lawrence, Michael S. Carter, Scott L. Stewart, Chip Gabriel, Stacey B. Meyerson, Matthew L. Beroukhim, Rameen Getz, Gad Lander, Eric Steven |
| author_sort | Drier, Yotam |
| collection | MIT |
| description | Whole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair 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. |
| first_indexed | 2024-09-23T09:03:01Z |
| format | Article |
| id | mit-1721.1/80787 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:03:01Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/807872022-09-30T13:04:08Z Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability Drier, Yotam Lawrence, Michael S. Carter, Scott L. Stewart, Chip Gabriel, Stacey B. Meyerson, Matthew L. Beroukhim, Rameen Getz, Gad Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. Whole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair 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. 2013-09-18T14:19:06Z 2013-09-18T14:19:06Z 2012-11 2012-10 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/80787 Drier, Y., M. S. Lawrence, S. L. Carter, C. Stewart, S. B. Gabriel, E. S. Lander, M. Meyerson, R. Beroukhim, and G. Getz. “Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability.” Genome Research 23, no. 2 (February 1, 2013): 228-235. en_US http://dx.doi.org/10.1101/gr.141382.112 Genome Research Creative Commons Attribution http://creativecommons.org/licenses/by-nc/3.0/ application/pdf Cold Spring Harbor Laboratory Press Genome Research |
| spellingShingle | Drier, Yotam Lawrence, Michael S. Carter, Scott L. Stewart, Chip Gabriel, Stacey B. Meyerson, Matthew L. Beroukhim, Rameen Getz, Gad Lander, Eric Steven Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title | Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title_full | Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title_fullStr | Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title_full_unstemmed | Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title_short | Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability |
| title_sort | somatic rearrangements across cancer reveal classes of samples with distinct patterns of dna breakage and rearrangement induced hypermutability |
| url | http://hdl.handle.net/1721.1/80787 |
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