Abstract 2175: Identification of Somatic BRCA1/2 mutation profile in tissue-based and liquid biopsy-based next generation sequencing in Egyptian patients with breast cancer
Authors: Lotfy Mai M. , Youssef Amira Salah El-Din , Nassar Auhood , Kamel Mahmoud , Hassan Zeinab K. , Abou-Bakr Amany Abd-Elhameed , Farahat Ahmed , Gomaa Mohamed M. , Zekri Abdel Rahman N. 
Published: July 2021

Abstract
Aim: Identification of BRCA1/2 mutations in Breast Cancer (BC) patients may help in providing genetic information to customize the therapeutic management of patients. Assessing liquid biopsies for BRCA1/2 somatic mutations could overcome the limitation of information gained from tissue biopsy. Consequently, this study aimed to identify the frequencies of pathogenic BRCA1 & BRCA2 somatic mutations in both liquid and tissue biopsies in Egyptian BC patients.
Material and methods: The study was conducted on 45 BC patients. Liquid and tissue biopsies were collected from each patient and they were profiled for BRCA1/2 mutations using next generation sequencing (NGS). Qiaseq UMI-based targeted panel was used for performing libraries. Ion proton platform was used for sequencing. The detected genetic variants at depth of coverage 500x were annotated against Cosmic, dbSNP, and Exac all databases. Polyphen-2, Sift prediction tools and Clinvar database were used to detect the biological function of the detected variants using IVA software.
Results: Variants analysis revealed that Among 45 patients, 37 (82.2%) patients were carrying one or more damaging BRCA1/2 somatic mutations. A total number of BRCA1/2 somatic variants detected was 24 and they were classified to 13 pathogenic, 7 likely pathogenic and 4 benign variants. Tissue and plasma samples of BC patients were found to harbor one detectable pathogenic somatic mutation in BRCA1 gene; c.1961delA with frequencies of 75.5% vs 17.7%, respectively. While, both samples had 8 detectable pathogenic BRCA2 somatic variants, the top 3 most frequent mutations among them were: c.5351delA (82.2% vs 40%), c.2957delA (75.56% vs 42.2%) and c.9253delA (68.89% vs 24.4%). One deleterious variant was detected merely in tissue sample; c.8940delA (55.5%). Whereas, 3 damaging variants were detected merely in plasma samples: c.8053delA (22.2%), c.6762delT (20%), c.4631delA (6.6%).Likely pathogenic BRCA2 somatic variants were also identified in both samples; c.7177delA (71.1% vs 53.3%) and c.10248delA (37.7% vs 11.1%). Moreover, 5 likely pathogenic variants were merely found in plasma samples. The most frequently detected variant among them was c.1114A&gt;C (42.2%). Our data showed that exon 10 in BRCA1 and exon 11 in BRCA2 are the most affected exons as they harbored the most frequent detected pathogenic variants.
Conclusion: Our preliminary results showed the most frequent pathogenic and likely pathogenic BRCA1/2 somatic mutations in liquid and tissue biopsies in Egyptian BC patients. This data may help in developing personalized targeted therapies that efficiently target the BRCA1/2 mutations.
Citation Format: Mai M. Lotfy, Amira Salah El-Din Youssef, Auhood Nassar, Mahmoud Kamel, Zeinab K. Hassan, Amany Abd-Elhameed Abou-Bakr, Ahmed Farahat, Mohamed M. Gomaa, Abdel Rahman N. Zekri. Identification of Somatic BRCA1/2 mutation profile in tissue-based and liquid biopsy-based next generation sequencing in Egyptian patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2175.