Characterization of the somatic landscape and transcriptional profile of breast tumors from 748 Hispanic/Latina women in California

ABSTRACT Somatic mutations and the tumor immune microenvironment (TIME) in breast tumors are important predictors of treatment response and survival, yet data for Hispanic/Latina (H/L) women are limited. Here we analyzed whole exome sequencing data from tumor/normal pairs and RNAseq data from 748 H/L women and 388 non-Hispanic White (NHW) women. Despite very similar somatic mutational and copy number profiles, we found significant differences in TIME ecotypes. TIME ecotypes CE9 and CE10, characterized by increased lymphocyte infiltration and more favorable prognosis, were more common among women with higher Indigenous American (IA) ancestry. A germline APOBEC3A/B copy-number deletion, significantly more common in H/L than NHW women, was associated with APOBEC mutational signatures and with CE10 ecotype. The APOBEC3A/B copy-number deletion was associated with overexpression of transposable elements (TEs) and TEs were strong predictors of CE10 ecotype. This suggests that the APOBEC3A/B and CE10 association may be driven via the disinhibition of these TEs. Overall, these results demonstrate the utility of characterizing previously understudied populations to infer new mechanisms of cancer immune responses.