| Автор | Shah, Sohrab P. |
| Автор | Roth, Andrew |
| Автор | Goya, Rodrigo |
| Автор | Oloumi, Arusha |
| Автор | Ha, Gavin |
| Автор | Zhao, Yongjun |
| Автор | Turashvili, Gulisa |
| Автор | Ding, Jiarui |
| Автор | Tse, Kane |
| Автор | Haffari, Gholamreza |
| Автор | Bashashati, Ali |
| Автор | Prentice, Leah M. |
| Автор | Khattra, Jaswinder |
| Автор | Burleigh, Angela |
| Автор | Yap, Damian |
| Автор | Bernard, Virginie |
| Автор | McPherson, Andrew |
| Автор | Shumansky, Karey |
| Автор | Crisan, Anamaria |
| Автор | Giuliany, Ryan |
| Автор | Heravi-Moussavi, Alireza |
| Автор | Rosner, Jamie |
| Автор | Lai, Daniel |
| Автор | Birol, Inanc |
| Автор | Varhol, Richard |
| Автор | Tam, Angela |
| Автор | Dhalla, Noreen |
| Автор | Zeng, Thomas |
| Автор | Ma, Kevin |
| Автор | Chan, Simon K. |
| Автор | Griffith, Malachi |
| Автор | Moradian, Annie |
| Автор | Cheng, S.-W. Grace |
| Автор | Morin, Gregg B. |
| Автор | Watson, Peter |
| Автор | Gelmon, Karen |
| Автор | Chia, Stephen |
| Автор | Chin, Suet-Feung |
| Автор | Curtis, Christina |
| Автор | Rueda, Oscar M. |
| Автор | Pharoah, Paul D. |
| Автор | Damaraju, Sambasivarao |
| Автор | Mackey, John |
| Автор | Hoon, Kelly |
| Автор | Harkins, Timothy |
| Автор | Tadigotla, Vasisht |
| Автор | Sigaroudinia, Mahvash |
| Автор | Gascard, Philippe |
| Автор | Tlsty, Thea |
| Автор | Costello, Joseph F. |
| Автор | Meyer, Irmtraud M. |
| Автор | Eaves, Connie J. |
| Автор | Wasserman, Wyeth W. |
| Автор | Jones, Steven |
| Автор | Huntsman, David |
| Автор | Hirst, Martin |
| Автор | Caldas, Carlos |
| Автор | Marra, Marco A. |
| Автор | Aparicio, Samuel |
| Дата выпуска | 2012 |
| dc.description | Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first timeâ to our knowledgeâ in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. |
| Формат | application.pdf |
| Издатель | Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
| Копирайт | Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
| Название | The clonal and mutational evolution spectrum of primary triple-negative breast cancers |
| Тип | LETTERS TO NATURE |
| DOI | 10.1038/nature10933 |
| Print ISSN | 0028-0836 |
| Журнал | Nature |
| Аффилиация | Shah, Sohrab P.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Roth, Andrew; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Goya, Rodrigo; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Oloumi, Arusha; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Ha, Gavin; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Zhao, Yongjun; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Turashvili, Gulisa; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Ding, Jiarui; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Tse, Kane; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Haffari, Gholamreza; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Bashashati, Ali; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Prentice, Leah M.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Khattra, Jaswinder; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Burleigh, Angela; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Yap, Damian; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Bernard, Virginie; Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada |
| Аффилиация | McPherson, Andrew; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Shumansky, Karey; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Crisan, Anamaria; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Giuliany, Ryan; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Heravi-Moussavi, Alireza; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Rosner, Jamie; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Lai, Daniel; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Birol, Inanc; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Varhol, Richard; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Tam, Angela; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Dhalla, Noreen; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Zeng, Thomas; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Ma, Kevin; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Chan, Simon K.; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Griffith, Malachi; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Moradian, Annie; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Cheng, S.-W. Grace; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Morin, Gregg B.; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada |
| Аффилиация | Watson, Peter; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada |
| Аффилиация | Gelmon, Karen; British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada |
| Аффилиация | Chia, Stephen; British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada |
| Аффилиация | Chin, Suet-Feung; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK |
| Аффилиация | Curtis, Christina; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA |
| Аффилиация | Rueda, Oscar M.; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK |
| Аффилиация | Pharoah, Paul D.; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK |
| Аффилиация | Damaraju, Sambasivarao; Departments of Oncology and Laboratory Medicine and Pathology, University of Alberta, 11560 University Avenue, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada |
| Аффилиация | Mackey, John; Departments of Oncology and Laboratory Medicine and Pathology, University of Alberta, 11560 University Avenue, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada |
| Аффилиация | Hoon, Kelly; Life Technologies, 101 Lincoln Centre Dr., Foster City, California 94404, USA |
| Аффилиация | Harkins, Timothy; Life Technologies, 101 Lincoln Centre Dr., Foster City, California 94404, USA |
| Аффилиация | Tadigotla, Vasisht; Life Technologies, 101 Lincoln Centre Dr., Foster City, California 94404, USA |
| Аффилиация | Sigaroudinia, Mahvash; Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA |
| Аффилиация | Gascard, Philippe; Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA |
| Аффилиация | Tlsty, Thea; Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA |
| Аффилиация | Costello, Joseph F.; Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA |
| Аффилиация | Meyer, Irmtraud M.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada; Department of Computer Science, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada; Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada |
| Аффилиация | Eaves, Connie J.; Terry Fox Laboratory, BC Cancer Agency, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada |
| Аффилиация | Wasserman, Wyeth W.; Centre for Molecular Medicine and Therapeutics, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada |
| Аффилиация | Jones, Steven; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr., Burnaby, British Columbia V5A1S6, Canada |
| Аффилиация | Huntsman, David; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada; Centre for Translational and Applied Genomics, BC Cancer Agency, 600 West 10th Ave, Vancouver, British Columbia V5Z 4E6, Canada |
| Аффилиация | Hirst, Martin; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada; Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada |
| Аффилиация | Caldas, Carlos; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK; Cambridge Breast Unit, Addenbrookes Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK; Cambridge Experimental Cancer Medicine Centre (ECMC), Cambridge CB2 0RE, UK |
| Аффилиация | Marra, Marco A.; Canadaâ s Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada |
| Аффилиация | Aparicio, Samuel; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada |
