Abstract 3014: Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients
Authors: Loutfy Samah , Najar Rania Abdulmonem Al , ElSayed Sarah , Fattah Nasra Abdel , Gaber Ayman Abdel-Samie , Hashem Tarek , Khalaf Wafaa S. , Basyony Ahmed F. , El-Sharif Amany , Radwan Sahar Mohamed Ramzy , Eltokhy Mohamed 
Published: March 2024

Abstract
Background: Recognizing the complexity of viral carcinogenesis and its perspectives, we aimed to investigate one of the key genetic factors associated with breast cancer development, BRCA1,2 mutations, and its association with the presence of some oncogenic viruses like HPV, MMTV, and EBV DNAs in both blood and tissues of breast cancer (BC) patients, hoping to provide new insights on role of oncogenic viruses in cancer development.
Patients and Methods: This study was conducted on 84 tissues and blood samples from Egyptian BC women and 50 blood samples from controls without known oncological disease. All samples were tested for the presence of viral DNAs, using real-time PCR assay. Fifty-five BC patients were investigated for the presence of mutations in exons 6 and 9 of BRCA1, and exons 11, 14, and 27 of BRCA2 using a high-resolution melting (HRM) assay. Results were correlated with the clinicopathological characteristics of BC. Results. HPV, MMTV, and EBV DNAs were detected in 30(35.7%), 19(22.6%), and 23 (27.3%) of tissues obtained from 84 BC patients, respectively, and into 16 (19%), 14 (16.7%) and 0 (0%) of blood from the same patients, respectively. On the other hand, these viruses were detected in 0 (0%), 7 (14%), and 0 (0%) of blood specimens obtained from 50 normal controls, respectively. Among 55 BC patients, mutations were detected in 37 (67%) of the tested exons of BRCA1/2 genes in the blood of BC patients, divided as 7 (12.7%) for exons 6 and 9 of BRCA1 gene, and into 11 (20%), 3 (5.5%), and 9 (16.4%) for exons 11, 14 and 27 of BRCA2 gene. Our previous investigation based on NGS showed that pathogenic mutations were (G509A:p.R170Q and c.C1471T:p.Q491X) for exons 6, 9 of BRCA1, respectively, and were (cT4001A: p.L1334X, c.7231delA: p.T2412Lfs and c.T9861A: p.C3287x) for exons 11, 14 and 27 of BRCA2, respectively. Further analysis showed that half of the patients with positive HPV DNA in tissues had mutations in the tested exons of BRCA1/2 genes. In contrast, none of the patients with MMTV DNA (15/55 (27%)) in their tissues had mutations in exons 6 and 9 of BRCA1 and only one patient had a mutation in exons 11 of BRCA2. Regarding EBV, 35% of positive patients had mutations in the tested exons of the BRCA1 gene and 21% in the tested exons of BRCA2 gene. Results were not affected by clinicopathological parameters.
Conclusion: MMTV DNA followed HPV, and then EBV DNAs were detected in more than 80% of our BC patients. HPV was the most frequent virus among BC patients showed to be associated with BRCA1/2 mutations in the tested exons. Sequencing analysis is in progress. Understanding this association will provide a relevant implication for developing novel, and personalized therapeutic options for treatment of oncogenic viruses.
Citation Format: Samah Loutfy, Rania Abdulmonem Al Najar, Sarah ElSayed, Nasra Abdel Fattah, Ayman Abdel-Samie Gaber, Tarek Hashem, Wafaa S. Khalaf, Ahmed F. Basyony, Amany El-Sharif, Sahar Mohamed Ramzy Radwan, Mohamed Eltokhy. Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3014.