Sequence analysis of mutations and translocations across breast cancer subtypes
| Autor: | Alex Toker, Abbie M. Frederick, Alex H. Ramos, Kristian Cibulskis, Nam Pho, Verónica Bautista-Piña, Valeria Quintanar-Jurado, Eric S. Lander, Kornelia Polyak, Claudia Rangel-Escareño, Sergio Rodriguez-Cuevas, José Baselga, Kristin K. Brown, Sandra Romero-Cordoba, Antonio Maffuz-Aziz, Shouyong Peng, Jorge Melendez-Zajgla, Rameen Beroukhim, Michael S. Lawrence, Alfredo Hidalgo-Miranda, Stacey Gabriel, Dennis C. Sgroi, Gerardo Jimenez-Sanchez, Andrea L. Richardson, Daniel Auclair, Gad Getz, Nicolas Stransky, Andrey Sivachenko, Rosa Rebollar-Vega, Fujiko Duke, Melissa Parkin, Todd R. Golub, Levi A. Garraway, Juan Carlos Fernández-López, Maria L. Cortes, Lihua Zou, Joonil Jung, Robert C. Onofrio, Laura Uribe-Figueroa, Kristin G. Ardlie, Kristin Thompson, Shantanu Banerji, Scott L. Carter, Joshua M. Francis, Matthew Meyerson, Carrie Sougnez, Steven E. Schumacher |
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| Rok vydání: | 2012 |
| Předmět: |
DNA Copy Number Variations
DNA Mutational Analysis Breast Neoplasms MAP3K1 Biology medicine.disease_cause Core Binding Factor beta Subunit Article Translocation Genetic Evolution Molecular Fusion gene Aromatase Breast cancer medicine Humans Exome skin and connective tissue diseases Mexico Gene Genetics Mutation Multidisciplinary Aromatase Inhibitors Genome Human Gene Expression Profiling Membrane Proteins Cancer Oncogenes medicine.disease Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Vietnam Mutagenesis Core Binding Factor Alpha 2 Subunit Female Gene Fusion Breast carcinoma Proto-Oncogene Proteins c-akt Algorithms |
| Zdroj: | Nature. 486:405-409 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Breast carcinoma is the leading cause of cancer-related mortality in women worldwide with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone1. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis, and responses to available therapy2–4. Recurrent somatic alterations in breast cancer have been described including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration5. Prior DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements 6–10. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA11, TP536, AKT112, GATA313, and MAP3K110, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking estrogen and progesterone receptors and ERBB2 expression. The Magi3-Akt3 fusion leads to constitutive activation of Akt kinase, which is abolished by treatment with an ATP-competitive Akt small-molecule inhibitor. |
| Databáze: | OpenAIRE |
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