Targeted Next Generation Sequencing of a Custom Capture Panel to Target Sequence 112 Cancer Related Genes in Breast Cancer Tumors ERBB2 Positive from Lleida (Spain)

Abstract

Between 15–30% of invasive breast cancers have ERBB2 gene amplifications. Even though such homogeneous group, every patient has their own prognosis based on different features, some of which genetic involved. With that aim, we implemented a custom NGS panel comprising three probe subgroups for testing targeted mutations, copy number alteration and translocation in tumors with known HR and ERBB2 status previously assessed via immunohistochemistry and fluorescence in situ hybridization. DNA extracted from 47 primary breast cancers previously classified as ERBB2 positive were analyzed with a customized panel of 112 cancer related genes by targeted sequencing. Output data on fastq format was qualified, aligned and variant called trough different algorithms to find gene variations. A total of 20 different pathogenic mutations were found in 44% of tumors. Copy number analysis showed different levels of ERBB2 gene amplifications between tumors as so as different ERBB2 amplicon lengths. Additionally, the analysis of the raw data revealed the existence of two distinct mutation signatures. The identification of gene variations schemes that can yield distinct signatures holds the potential to accurately predict the subset of ERBB2-positive breast cancer patients who would respond best to treatment, specifically based on their pathological complete response (pCR).