The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes
The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2016
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| Online Access: | https://eprints.nottingham.ac.uk/37693/ |
| _version_ | 1848795513453805568 |
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| author | Pereira, Bernard Chin, Suet-Feung Rueda, Oscar M. Vollan, Hans-Kristian Moen Provenzano, Elena Bardwell, Helen A. Pugh, Michelle Jones, Linda Russell, Roslin Sammut, Stephen-John Tsui, Dana W.Y. Liu, Bin Dawson, Sarah-Jane Abraham, Jean Northen, Helen Peden, John F. Mukherjee, Abhik Turashvili, Gulisa Green, Andrew R. McKinney, Steve Oloumi, Arusha Shah, Sohrab Rosenfeld, Nitzan Murphy, Leigh Bentley, David R. Ellis, Ian O. Purushotham, Arnie Pinder, Sarah E. Børresen-Dale, Anne-Lise Earl, Helena M. Pharoah, Paul D. Ross, Mark T. Aparicio, Samuel Caldas, Carlos |
| author_facet | Pereira, Bernard Chin, Suet-Feung Rueda, Oscar M. Vollan, Hans-Kristian Moen Provenzano, Elena Bardwell, Helen A. Pugh, Michelle Jones, Linda Russell, Roslin Sammut, Stephen-John Tsui, Dana W.Y. Liu, Bin Dawson, Sarah-Jane Abraham, Jean Northen, Helen Peden, John F. Mukherjee, Abhik Turashvili, Gulisa Green, Andrew R. McKinney, Steve Oloumi, Arusha Shah, Sohrab Rosenfeld, Nitzan Murphy, Leigh Bentley, David R. Ellis, Ian O. Purushotham, Arnie Pinder, Sarah E. Børresen-Dale, Anne-Lise Earl, Helena M. Pharoah, Paul D. Ross, Mark T. Aparicio, Samuel Caldas, Carlos |
| author_sort | Pereira, Bernard |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. |
| first_indexed | 2025-11-14T19:33:17Z |
| format | Article |
| id | nottingham-37693 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:33:17Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-376932020-05-04T17:52:29Z https://eprints.nottingham.ac.uk/37693/ The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes Pereira, Bernard Chin, Suet-Feung Rueda, Oscar M. Vollan, Hans-Kristian Moen Provenzano, Elena Bardwell, Helen A. Pugh, Michelle Jones, Linda Russell, Roslin Sammut, Stephen-John Tsui, Dana W.Y. Liu, Bin Dawson, Sarah-Jane Abraham, Jean Northen, Helen Peden, John F. Mukherjee, Abhik Turashvili, Gulisa Green, Andrew R. McKinney, Steve Oloumi, Arusha Shah, Sohrab Rosenfeld, Nitzan Murphy, Leigh Bentley, David R. Ellis, Ian O. Purushotham, Arnie Pinder, Sarah E. Børresen-Dale, Anne-Lise Earl, Helena M. Pharoah, Paul D. Ross, Mark T. Aparicio, Samuel Caldas, Carlos The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. Nature Publishing Group 2016-05-10 Article PeerReviewed Pereira, Bernard, Chin, Suet-Feung, Rueda, Oscar M., Vollan, Hans-Kristian Moen, Provenzano, Elena, Bardwell, Helen A., Pugh, Michelle, Jones, Linda, Russell, Roslin, Sammut, Stephen-John, Tsui, Dana W.Y., Liu, Bin, Dawson, Sarah-Jane, Abraham, Jean, Northen, Helen, Peden, John F., Mukherjee, Abhik, Turashvili, Gulisa, Green, Andrew R., McKinney, Steve, Oloumi, Arusha, Shah, Sohrab, Rosenfeld, Nitzan, Murphy, Leigh, Bentley, David R., Ellis, Ian O., Purushotham, Arnie, Pinder, Sarah E., Børresen-Dale, Anne-Lise, Earl, Helena M., Pharoah, Paul D., Ross, Mark T., Aparicio, Samuel and Caldas, Carlos (2016) The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nature Communications, 7 . 11479/1-11479/15. ISSN 2041-1723 http://www.nature.com/articles/ncomms11479 doi:10.1038/ncomms11479 doi:10.1038/ncomms11479 |
| spellingShingle | Pereira, Bernard Chin, Suet-Feung Rueda, Oscar M. Vollan, Hans-Kristian Moen Provenzano, Elena Bardwell, Helen A. Pugh, Michelle Jones, Linda Russell, Roslin Sammut, Stephen-John Tsui, Dana W.Y. Liu, Bin Dawson, Sarah-Jane Abraham, Jean Northen, Helen Peden, John F. Mukherjee, Abhik Turashvili, Gulisa Green, Andrew R. McKinney, Steve Oloumi, Arusha Shah, Sohrab Rosenfeld, Nitzan Murphy, Leigh Bentley, David R. Ellis, Ian O. Purushotham, Arnie Pinder, Sarah E. Børresen-Dale, Anne-Lise Earl, Helena M. Pharoah, Paul D. Ross, Mark T. Aparicio, Samuel Caldas, Carlos The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title | The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title_full | The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title_fullStr | The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title_full_unstemmed | The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title_short | The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| title_sort | somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes |
| url | https://eprints.nottingham.ac.uk/37693/ https://eprints.nottingham.ac.uk/37693/ https://eprints.nottingham.ac.uk/37693/ |