Comprehensive germline and somatic profiling of high-risk Thai breast cancer via next-generation sequencing

Breast cancer genomic landscapes differ across ethnic groups, yet the somatic profile of Thai breast tumours has remained uncharacterised. This study analysed 1676 high-hereditary-risk Thai breast cancer patients, identified according to National Comprehensive Cancer Network (NCCN) guideline. Germline alterations were assessed in 1370 cases using a custom 36-core cancer panel. Somatic mutations were characterised in formalin-fixed, paraffin-embedded tumour tissues from 180 of the 1676 patients using the 501-gene Oncomine Comprehensive Assay Plus panel. Pathogenic or likely pathogenic (P/LP) variants were detected in 13% of the 1370 germline analyses, with BRCA1 and BRCA2 being the most frequently altered genes. The prevalence of P/LP variants in BRCA1, BRCA2, and PALB2 differed from that observed in other ethnic cohorts. In somatic profiling, TP53 emerged as the most frequently mutated gene, especially in HER2 and TNBC tumours, whereas MAP3K1 and GATA3 were the most frequently mutated genes in the HR+/HER2- tumours. Moreover, hormone-receptor-positive (HR+) tumours showed distinct mutation patterns compared with other ethnicities. Notably, germline carriers exhibited lower PIK3CA mutation rates than non-carriers. These findings advance our understanding of Thai breast cancer genomics and underscore the importance of ethnic diversity in cancer research, offering insights into tailored screening and therapeutic approaches.