Different members of the APOBEC3 family of DNA mutators have opposing associations with the landscape of breast cancer

xlomafota13 shared this article with you from Inoreader Different members of the APOBEC3 family of DNA mutators have opposing associations with the landscape of breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5111-5125. eCollection 2021. ABSTRACT APOBEC enzymes are strong mutagenic factors. In breast cancer, expression of APOBEC3B is increased and associated with mutation load and poor outcome. Other APOBEC3s can also mutate DNA but their clinical significance in breast cancer and its underpinnings have not been comprehensively studied. In our examination of 1,091 breast carcinoma cases, high expression of APOBEC3A or APOBEC3B genes was associated with greater tumor burden of mutations and other genomic aberrations. Expression of none of the five APOBEC3C-H genes had any correlation with these features, including T[C-T/G]W mutations, but their high expression levels indicated a robust anti-cancer immune response within tumors, with elevated CD8+ T cell abundance, T cell receptor diversity, and immune cytolytic activity. Concordantly, survival analyses of this and two other cohorts with > 3,000 patients each showed favorable prognostic benefit of high APOBEC3C-H expression for both cancer progression and mortality. A detrimental prognostic value was observed for APOBEC3A and APOBEC3B. Single-cell data revealed cancer epithelial and stromal immune cells as major sources of APOBEC3B and APOBEC3C-H expression in tumors, respectively. These observations on opposing associations with breast cancer of different APOBEC3s highlight the contrasting roles of these enzymes, promoting cancer through mutagenesis while antagonizing it through immune response. PMID:34765315 | PMC:PMC8569370 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.