M6A Pathway Regulators Are Frequently Mutated in Breast Invasive Carcinoma and May Play an Important Role in Disease Pathogenesis.

Abstract

Breast invasive carcinoma (BIC) is one of the most commonly observed and the deadliest cancer among women. Studies examining the role of epigenetics and regulation of gene expression stand to make important strides in clinical management of BIC. In this context, messenger-RNA (mRNA) modification by regulatory proteins is noteworthy. Methylation of the adenosine base on the sixth nitrogen position is termed as N6-methyladenosine (m6A) modification, and this is the most abundant mRNA modification in mammals. Using several publicly available datasets, we report, in this study, comprehensive analyses and new findings on the impact of epitranscriptome regulatory factors and genetic alterations in m6A pathway genes on BIC. Accordingly, mutation frequency, type, and expression levels were determined. Importantly, we found that VIRMA, METTL14, RBM15B, EIF3B, YTHDF1, and YTHDF3 genes hold potential significance as prognostic biomarker candidates as evidenced in particular by the overall survival analysis. Enrichment of gene ontology (GO) terms and KEGG pathways for the tumor samples with genetic alterations in the epitranscriptome regulatory pathways were investigated. Dysregulation of regulatory factors in breast cancer was associated with cell division, and survival-related pathways such as "nuclear division," and "chromosome segregation." Hence, the gained overactivity of these pathways may account for BIC's poor prognosis. In conclusion, these data underscore that m6A pathway regulators are frequently mutated in BIC and likely play a significant role in disease pathogenesis. Epitranscriptome pathway genes warrant further research attention as regulators of cancer growth and biological targets in BIC, and with an eye to personalized medicine in clinical oncology.