Epigenetic heterogeneity and transcriptional drivers of triple-negative breast cancer

ABSTRACT: Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity, we defined transcriptional, epigenetic, and metabolic subtypes, and subtype-driving super-enhancers and transcription factors by combining functional and molecular profiling with computational analyses. Single cell RNA sequencing revealed relative homogeneity of the major transcriptional subtypes (luminal, basal, and mesenchymal) within samples. We found that mesenchymal TNBCs are more similar to mesenchymal neuroblastoma and rhabdoid tumors than to other TNBC subtypes, and the PRRX1 transcription factor is a key driver of these tumors. PRRX1 is sufficient for inducing mesenchymal features in basal but not in luminal TNBC cells via reprogramming cellular super-enhancer landscapes and transcriptome but it is not required for its maintenance and for cellular viability. Our comprehensive, large scale, multi-platform, multi-omics study of both experimental and clinical TNBC is an excellent resource for the scientific and clinical research communities as it opens new venues for future investigations.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Kornelia Polyak  

PROVIDER: MSV000091071 | MassIVE | Tue Jan 17 10:17:00 GMT 2023

REPOSITORIES: MassIVE