Polak P, Kim J, Braunstein LZ, Karlic R, Haradhavala NJ, Tiao G, Rosebrock D, Livitz D, Kubler K, Mouw KW, et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat Genet. 2017;49:1476–1486.
NOTES
Polak, PazKim, JaegilBraunstein, Lior ZKarlic, RosaHaradhavala, Nicholas JTiao, GraceRosebrock, DanielLivitz, DimitriKubler, KirstenMouw, Kent WKamburov, AtanasMaruvka, Yosef ELeshchiner, IgnatyLander, Eric SGolub, Todd RZick, AviadOrthwein, AlexandreLawrence, Michael SBatra, Rajbir NCaldas, CarlosHaber, Daniel ALaird, Peter WShen, HuiEllisen, Leif WD'Andrea, Alan DChanock, Stephen JFoulkes, William DGetz, GadengU24 CA143845/CA/NCI NIH HHS/Nat Genet. 2017 Oct;49(10):1476-1486. doi: 10.1038/ng.3934. Epub 2017 Aug 21.
Abstract
Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing approximately 1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation is strongly associated with signature 3 and, in our data set, was highly enriched in basal-like breast cancers in young individuals of African descent.
Last updated on 02/17/2021