TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects

Abstract

Recent genomics studies of breast cancer in Asian cohorts have found a higher prevalence of TP53 mutations in Asian breast cancer patients relative to Caucasian patients. However, the effect of TP53 mutations on Asian breast tumours has not been comprehensively studied. Here, we report an analysis of 492 breast cancer samples from the Malaysian Breast Cancer (MyBrCa) cohort where we examined the impact of TP53 somatic mutations in relation to PAM50 subtypes by comparing whole exome and transcriptome data from tumours with mutant and wild type TP53. We found that the magnitude of impact of TP53 somatic mutations appears to vary between different subtypes. TP53 somatic mutations were associated with larger and more consistent differences in HR deficiency scores as well as transcriptional alterations in the luminal A and luminal B subtypes compared to the basal-like and Her2-enriched subtypes. The only pathways that were consistently dysregulated when comparing tumours with mutant and wild type TP53 across the different subtypes were the mTORC1 signaling and glycolysis pathways. These results suggest that therapies that target TP53 or other downstream pathways may be more effective against luminal A and B tumours in the Asian population.