DNA methylation landscape of primary triple-negative breast cancer

A study recently published on Nature Communications, by investigating the DNA methylation landscape of triple-negative breast cancer (TNBC), defines two epigenetic subtypes of TNBC with different transcriptional patterns and also different immunological microenvironments and immune evasion strategies.

Authors analyzed tumor methylome profiles of 235 patients with TNBC; they collected complete whole genome sequencing, RNA sequencing, BRCA1 hypermethylation status, global DNA methylation profiles, in situ immunohistochemistry data, morphological assessments, and extensive treatment and clinical follow-up data. Based on methylation data and the genomic context of CpG methylation, authors divided TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group; these groups had characteristic transcriptional patterns correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Moreover, they showed different immunological microenvironments, putative epigenetically-mediated immune evasion strategies, and a specific metabolic gene network in older patients that may be epigenetically regulated. Authors postulated the existence of two major epigenetic backbones in TNBC, a Basal and a nonBasal epitype, that should represent distinct DNA methylation ground states of the disease and that may in turn be further subdivided into subgroups with seemingly distinct metabolic and immune-evasive strategies. Results of this study highlighted plausible epigenetic regulation of important pioneering factors in breast cancer that may help to explain key transcriptional differences between Basal and nonBasal breast cancer irrespective of clinical subgroups. «Based on our results, further research should be directed towards understanding the cell of origin of the epigenetic backbones, links between the epigenetic phenotypes and immune evasion strategies, and metabolic differences within the transcriptional and epigenetic subtypes of TNBC», authors conclude.