Somatic mutation profiling of breast cancer by next-generation sequencing

Abstract

Background: Despite the prominence in estimating cancer risk and risk-reducing intervention, lots of data support the improvement of disease free survival and overall survival through targeted therapy. Tumour profiling plays an important role in precision medicine and might provide markers for monitoring on therapeutic responses and relapse with possibly liquid biopsies. Considering the variations in mutation spectrum across ethnicity, it is worth studying the mutation profiling in Chinese population for future drug developments. Methods: High risk breast cancer patients who were germline negative (BRCA1, BRCA2, TP53 and PTEN) were selected from Hong Kong Hereditary Breast Cancer Family Registry. 81 tumor DNA was subjected to 93 genes breast cancer panel by next-generation sequencing (NGS). Sequencing data were then analyzed by our in-house developed bioinformatic pipeline. Result: Fifty one pathogenic/likely pathogenic variants and 18 VUS were identified, which correspond to 45 patients and 12 cancer predisposition genes. The most common mutated genes were TP53 (33.33%), PIK3CA (30.43%) and PTEN (7.25%). Among 45 patients with mutations, 26 patients (57.8%) identified a potential actionable drug target. Conclusions: Our data suggests that NGS is useful in 57.8% of the cases, and one-third of the patients may benefit from targeted therapy. Different from ovarian cancer, neither BRCA1 nor BRCA2 somatic mutation has been detected. NGS allows better understanding of tumorigenesis which potentially broadens the therapeutic options and enhance molecular monitoring by liquid biopsy. The accumulated data contributes to a more comprehensive and applicable database of somatic mutation profiling in breast cancer of local population.