Sequence analysis of mutations and translocations across breast cancer subtypes

Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012;486:405–9.

NOTES

Banerji, ShantanuCibulskis, KristianRangel-Escareno, ClaudiaBrown, Kristin KCarter, Scott LFrederick, Abbie MLawrence, Michael SSivachenko, Andrey YSougnez, CarrieZou, LihuaCortes, Maria LFernandez-Lopez, Juan CPeng, ShouyongArdlie, Kristin GAuclair, DanielBautista-Pina, VeronicaDuke, FujikoFrancis, JoshuaJung, JoonilMaffuz-Aziz, AntonioOnofrio, Robert CParkin, MelissaPho, Nam HQuintanar-Jurado, ValeriaRamos, Alex HRebollar-Vega, RosaRodriguez-Cuevas, SergioRomero-Cordoba, Sandra LSchumacher, Steven EStransky, NicolasThompson, Kristin MUribe-Figueroa, LauraBaselga, JoseBeroukhim, RameenPolyak, KorneliaSgroi, Dennis CRichardson, Andrea LJimenez-Sanchez, GerardoLander, Eric SGabriel, Stacey BGarraway, Levi AGolub, Todd RMelendez-Zajgla, JorgeToker, AlexGetz, GadHidalgo-Miranda, AlfredoMeyerson, MatthewengCA089393/CA/NCI NIH HHS/U54 HG003067/HG/NHGRI NIH HHS/R01 CA122099/CA/NCI NIH HHS/P50 CA089393/CA/NCI NIH HHS/U24 CA143845/CA/NCI NIH HHS/Howard Hughes Medical Institute/CA122099/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tEnglandNature. 2012 Jun 20;486(7403):405-9. doi: 10.1038/nature11154.

Abstract

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.
Last updated on 02/17/2021