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

Ding, Y.; Sayaman, R. W.; Wolf, D.; Mortimer, J.; Mao, A.; Fejerman, L.; Gruber, S. B.; Neuhausen, S. L.; Ziv, E.

2026-02-17 genetic and genomic medicine
10.64898/2026.02.13.26346286 medRxiv
Show abstract

Somatic mutations and the tumor immune microenvironment 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. Overall, the somatic profiles in tumors from H/L women were similar to NHW women. However, somatic mutations in genome organizer CTCF were significantly more common in H/L women. We also found that tumor microenvironment immune ecotypes CE9 and CE10, characterized by increased lymphocyte infiltration and more favorable prognosis, were more common among women with higher Indigenous American ancestry. Finally, we found that a germline APOBEC3A/B copy-number deletion was more prevalent in H/L than in NHW and was associated with the COSMIC APOBEC mutational signatures and with CE10 ecotype. Overall, these results suggest that ancestry differences may provide insights into specific mutation and immune profiles.

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