Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer
Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androg...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/84658 |
| _version_ | 1826216314642890752 |
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| author | Barbieri, Christopher E. Baca, Sylvan C. Lawrence, Michael S. Demichelis, Francesca Blattner, Mirjam Theurillat, Jean-Philippe White, Thomas A. Stojanov, Petar Van Allen, Eliezer Stransky, Nicolas Nickerson, Elizabeth Chae, Sung-Suk Boysen, Gunther Auclair, Daniel Onofrio, Robert Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Sheikh, Karen Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Barbieri, Christopher E. Baca, Sylvan C. Lawrence, Michael S. Demichelis, Francesca Blattner, Mirjam Theurillat, Jean-Philippe White, Thomas A. Stojanov, Petar Van Allen, Eliezer Stransky, Nicolas Nickerson, Elizabeth Chae, Sung-Suk Boysen, Gunther Auclair, Daniel Onofrio, Robert Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Sheikh, Karen Lander, Eric Steven |
| author_sort | Barbieri, Christopher E. |
| collection | MIT |
| description | Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6–15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer. |
| first_indexed | 2024-09-23T16:45:47Z |
| format | Article |
| id | mit-1721.1/84658 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:45:47Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/846582022-10-03T08:06:47Z Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer Barbieri, Christopher E. Baca, Sylvan C. Lawrence, Michael S. Demichelis, Francesca Blattner, Mirjam Theurillat, Jean-Philippe White, Thomas A. Stojanov, Petar Van Allen, Eliezer Stransky, Nicolas Nickerson, Elizabeth Chae, Sung-Suk Boysen, Gunther Auclair, Daniel Onofrio, Robert Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Sheikh, Karen Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6–15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer. National Human Genome Research Institute (U.S.) (Large Scale Sequencing Program Grant U54 HG003067) 2014-02-03T20:16:49Z 2014-02-03T20:16:49Z 2012-05 2011-12 Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/84658 Barbieri, Christopher E, Sylvan C Baca, Michael S Lawrence, Francesca Demichelis, Mirjam Blattner, Jean-Philippe Theurillat, Thomas A White, et al. “Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.” Nature Genetics 44, no. 6 (May 20, 2012): 685-689. en_US http://dx.doi.org/10.1038/ng.2279 Nature Genetics Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Barbieri, Christopher E. Baca, Sylvan C. Lawrence, Michael S. Demichelis, Francesca Blattner, Mirjam Theurillat, Jean-Philippe White, Thomas A. Stojanov, Petar Van Allen, Eliezer Stransky, Nicolas Nickerson, Elizabeth Chae, Sung-Suk Boysen, Gunther Auclair, Daniel Onofrio, Robert Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Sheikh, Karen Lander, Eric Steven Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title_full | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title_fullStr | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title_full_unstemmed | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title_short | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer |
| title_sort | exome sequencing identifies recurrent spop foxa1 and med12 mutations in prostate cancer |
| url | http://hdl.handle.net/1721.1/84658 |
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