Recurrent and functional regulatory mutations in breast cancer
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cance...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/117280 https://orcid.org/0000-0002-5754-1719 |
| _version_ | 1826216345592659968 |
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| author | Parasuraman, Prasanna Tiao, Grace Kim, Jaegil Taylor-Weiner, Amaro Rodriguez-Cuevas, Sergio Rosenberg, Mara Hess, Julian Stewart, Chip Maruvka, Yosef E. Stojanov, Petar Seepo, Sara Cibulskis, Carrie Tracy, Adam Pugh, Trevor J. Lee, Jesse Zheng, Zongli Ellisen, Leif W. Iafrate, A. John Boehm, Jesse S. Baselga, Jose Hidalgo-Miranda, Alfredo Shioda, Toshi Bernards, Andre Engreitz, Jesse Michael Lander, Eric Steven Rheinbay, Esther Lawrence, Michael Cortes, Maria Gabriel, Stacey Golub, Todd Getz, Gad Asher Meyerson, Matthew L. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Parasuraman, Prasanna Tiao, Grace Kim, Jaegil Taylor-Weiner, Amaro Rodriguez-Cuevas, Sergio Rosenberg, Mara Hess, Julian Stewart, Chip Maruvka, Yosef E. Stojanov, Petar Seepo, Sara Cibulskis, Carrie Tracy, Adam Pugh, Trevor J. Lee, Jesse Zheng, Zongli Ellisen, Leif W. Iafrate, A. John Boehm, Jesse S. Baselga, Jose Hidalgo-Miranda, Alfredo Shioda, Toshi Bernards, Andre Engreitz, Jesse Michael Lander, Eric Steven Rheinbay, Esther Lawrence, Michael Cortes, Maria Gabriel, Stacey Golub, Todd Getz, Gad Asher Meyerson, Matthew L. |
| author_sort | Parasuraman, Prasanna |
| collection | MIT |
| description | Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients. |
| first_indexed | 2024-09-23T16:46:10Z |
| format | Article |
| id | mit-1721.1/117280 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:46:10Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1172802022-09-29T21:23:14Z Recurrent and functional regulatory mutations in breast cancer Parasuraman, Prasanna Tiao, Grace Kim, Jaegil Taylor-Weiner, Amaro Rodriguez-Cuevas, Sergio Rosenberg, Mara Hess, Julian Stewart, Chip Maruvka, Yosef E. Stojanov, Petar Seepo, Sara Cibulskis, Carrie Tracy, Adam Pugh, Trevor J. Lee, Jesse Zheng, Zongli Ellisen, Leif W. Iafrate, A. John Boehm, Jesse S. Baselga, Jose Hidalgo-Miranda, Alfredo Shioda, Toshi Bernards, Andre Engreitz, Jesse Michael Lander, Eric Steven Rheinbay, Esther Lawrence, Michael Cortes, Maria Gabriel, Stacey Golub, Todd Getz, Gad Asher Meyerson, Matthew L. Broad Institute of MIT and Harvard Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Engreitz, Jesse Michael Lander, Eric Steven Rheinbay, Esther Lawrence, Michael Cortes, Maria Gabriel, Stacey Meyerson, Matthew L Golub, Todd Getz, Gad Asher Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients. 2018-08-06T16:05:22Z 2018-08-06T16:05:22Z 2017-06 2016-04 2018-08-01T15:16:39Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/117280 Rheinbay, Esther et al. “Recurrent and Functional Regulatory Mutations in Breast Cancer.” Nature 547, 7661 (June 2017): 55–60 https://orcid.org/0000-0002-5754-1719 http://dx.doi.org/10.1038/NATURE22992 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Parasuraman, Prasanna Tiao, Grace Kim, Jaegil Taylor-Weiner, Amaro Rodriguez-Cuevas, Sergio Rosenberg, Mara Hess, Julian Stewart, Chip Maruvka, Yosef E. Stojanov, Petar Seepo, Sara Cibulskis, Carrie Tracy, Adam Pugh, Trevor J. Lee, Jesse Zheng, Zongli Ellisen, Leif W. Iafrate, A. John Boehm, Jesse S. Baselga, Jose Hidalgo-Miranda, Alfredo Shioda, Toshi Bernards, Andre Engreitz, Jesse Michael Lander, Eric Steven Rheinbay, Esther Lawrence, Michael Cortes, Maria Gabriel, Stacey Golub, Todd Getz, Gad Asher Meyerson, Matthew L. Recurrent and functional regulatory mutations in breast cancer |
| title | Recurrent and functional regulatory mutations in breast cancer |
| title_full | Recurrent and functional regulatory mutations in breast cancer |
| title_fullStr | Recurrent and functional regulatory mutations in breast cancer |
| title_full_unstemmed | Recurrent and functional regulatory mutations in breast cancer |
| title_short | Recurrent and functional regulatory mutations in breast cancer |
| title_sort | recurrent and functional regulatory mutations in breast cancer |
| url | http://hdl.handle.net/1721.1/117280 https://orcid.org/0000-0002-5754-1719 |
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