Punctuated Evolution of Prostate Cancer Genomes
The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/102247 |
| _version_ | 1811072531845611520 |
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| author | Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven |
| author_sort | Lander, Eric Steven |
| collection | MIT |
| description | The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term “chromoplexy,” frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. |
| first_indexed | 2024-09-23T09:07:20Z |
| format | Article |
| id | mit-1721.1/102247 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:07:20Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1022472022-09-30T13:35:16Z Punctuated Evolution of Prostate Cancer Genomes Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Lander, Eric S. The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term “chromoplexy,” frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. National Human Genome Research Institute (U.S.). Large Scale Sequencing Program (U54 HG003067) 2016-04-15T19:54:35Z 2016-04-15T19:54:35Z 2013-04 2013-01 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/102247 Baca, Sylvan C., Davide Prandi, Michael S. Lawrence, Juan Miguel Mosquera, Alessandro Romanel, Yotam Drier, Kyung Park, et al. “Punctuated Evolution of Prostate Cancer Genomes.” Cell 153, no. 3 (April 2013): 666–677. en_US http://dx.doi.org/10.1016/j.cell.2013.03.021 Cell Creative Commons Attribution-Noncommercial-NoDerivatives http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Lander, Eric Steven Punctuated Evolution of Prostate Cancer Genomes |
| title | Punctuated Evolution of Prostate Cancer Genomes |
| title_full | Punctuated Evolution of Prostate Cancer Genomes |
| title_fullStr | Punctuated Evolution of Prostate Cancer Genomes |
| title_full_unstemmed | Punctuated Evolution of Prostate Cancer Genomes |
| title_short | Punctuated Evolution of Prostate Cancer Genomes |
| title_sort | punctuated evolution of prostate cancer genomes |
| url | http://hdl.handle.net/1721.1/102247 |
| work_keys_str_mv | AT landerericsteven punctuatedevolutionofprostatecancergenomes |