Differential expression of histone cluster 3, H2a in triple negative breast cancer.
Women diagnosed with triple negative breast cancer are predicted to benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding histone cluster 3, H2a, HIST3H2A, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). HIST3H2A was also differentially expressed in bulk tumor in human breast cancer (3). HIST3H2A mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of HIST3H2A in primary tumors of the breast was correlated with recurrence-free survival in patients with luminal A and HER2+ type cancer, while within triple negative breast cancer, primary tumor expression of HIST3H2A was correlated with distant metastasis-free survival in patients with immunomodulatory, mesenchymal, and luminal androgen receptor subtype disease. HIST3H2A may be of relevance to initiation, maintenance or progression of triple negative breast cancers.