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Nature DOI:10.1038/nature11154

Sequence analysis of mutations and translocations across breast cancer subtypes.

Publication TypeJournal Article
Year of Publication2012
AuthorsBanerji, S, Cibulskis, K, Rangel-Escareño, C, Brown, KK, Carter, SL, Frederick, AM, Lawrence, MS, Sivachenko, AY, Sougnez, C, Zou, L, Cortés, ML, Fernandez-Lopez, JC, Peng, S, Ardlie, KG, Auclair, D, Bautista-Piña, V, Duke, F, Francis, J, Jung, J, Maffuz-Aziz, A, Onofrio, RC, Parkin, M, Pho, NH, Quintanar-Jurado, V, Ramos, AH, Rebollar-Vega, R, Rodriguez-Cuevas, S, Romero-Cordoba, SL, Schumacher, SE, Stransky, N, Thompson, KM, Uribe-Figueroa, L, Baselga, J, Beroukhim, R, Polyak, K, Sgroi, DC, Richardson, AL, Jimenez-Sanchez, G, Lander, ES, Gabriel, SB, Garraway, LA, Golub, TR, Melendez-Zajgla, J, Toker, A, Getz, G, Hidalgo-Miranda, A, Meyerson, M
Date Published2012 Jun 20
KeywordsAlgorithms, Breast Neoplasms, Core Binding Factor Alpha 2 Subunit, Core Binding Factor beta Subunit, DNA Mutational Analysis, Exome, Female, Gene Fusion, Humans, Membrane Proteins, Mexico, Mutation, Proto-Oncogene Proteins c-akt, Translocation, Genetic, Vietnam

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 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. 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 aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. 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 PIK3CA, TP53, AKT1, GATA3 and MAP3K1, 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 oestrogen 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.


Alternate JournalNature
PubMed ID22722202
PubMed Central IDPMC4148686
Grant ListCA089393 / CA / NCI NIH HHS / United States
R01 CA122099 / CA / NCI NIH HHS / United States
P50 CA089393 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
CA122099 / CA / NCI NIH HHS / United States