Phenotypic and Functional Characterization of Oncohistone Mutations in Breast Cancers [III]

Herein, we curated missense mutations occurring in core histone genes in breast cancers using data from MSK-IMPACT and cBioPortal to identify high frequency breast cancer-associated histone gene mutations.

We characterized 17 high frequency oncohistone mutations in H2A H2B, and H3 that are enriched in breast cancer samples and occurred at glutamate (E), aspartate (D), serine (S), and arginine (R) residues. Many of these mutants co-occur with PIK3CA mutations in breast cancer samples. The oncohistone mutants were expressed in MCF-7 breast cancer cells or MCF10A mammary epithelial cells and screened for effects on oncogenic phenotypes in a variety of cell- and tumor-based assays (i.e., proliferation, migration, invasion, competitive outgrowth, transformation).