Abstract P3-06-15: Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study

Abstract

Abstract Background: Identification of genomic alterations present in cancer patients can aid in improving cancer diagnosis and prognosis. In this study, we aimed to identify clinically actionable variations present in stage IV breast cancer (BC) samples. Methods: DNA was extracted from formalin fixed paraffin embedded samples of breast cancer (n=41). DNA was sequenced using MammaSeqTM, a breast cancer specific NGS panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data. Resulting single nucleotide variants (SNVs) were annotated using CRAVAT toolkit. CNVkit was employed to identify copy number variations (CNVs). The PMKB and OncoKB Precision Oncology Databases were used to associate clinical significance with the identified variants. Results: A total of 41 BC patient samples were sequenced (read depth of 94 - 13340, median of 1529). In total, 96 different alterations (84 SNVs and 12 CNVs) were identified. Frequent SNVs were seen in PIK3CA, TP53, IKBKE, ATM and MAP3K1 genes. Moreover, amplifications were found in ERBB2, FGFR and AR, and deletions in BRCA2, RUNX1 and RB1. 3 CNVs (ERRB2, FGFR and AR amplifications) and 7 SNVs (IDH1.R132H, TP53.E204*, AKT1.E17K, PI3KCA.E545K, PI3KCA.H1047R, PI3KCA.R88Q and ERBB2.V777L) were reported as clinically significant by PMKB and OncoKB. Conclusion: We identified 96 alterations in 50 genes in 41 stage IV BC tissue samples using MammaSeqTM. Ten of these alterations were reported as clinically significant. This study highlights the potential use of cancer specific NGS panels in clinic to get better insight into the cancer patient-specific genomic alterations. Citation Format: Atilla Soran, Mustafa Sahin, Serdar Ugras, Esin Celik, Osama Shiraz Shah, Peter C Lucas, Adrian V Lee. Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-15.