Abstract 2512: BRCA1 and BRCA2 mutations and its clinical relevance among egyptian breast cancer women
Authors: Loutfy Samah A. , Fattah Nasra F. Abdel , Barakat Ahmed B. , Alfarouk Omar R. , Hashem Tarek M. , Osman Ahmed M. , Metwally Shimaa A. , Abo-Shadi Maha A. , Helal Amany M. , Habib Shaza A. , Sherif Ahmed A. El , Ghareeb Abdel Wahab El , Mouneer Mohamed M. , Moneer Manar M. , Abdel-Wahed Marwa A. , Salem Mona A. , Salama Asmaa M. M. M. , Hafez Fatma S. , Agwa Sara H. , Elghazaly Hesham , El-Mahdy Manal M. , Dunning Mark J. , El-Khamisy Sherif F. 
Published: July 2021

Introduction: Breast cancer (BC) is a multifactorial disease, that is attributed to non-familial factors such as environmental or genetic factors that play a vital role in the development of the disease. BRCA1/2 mutations represent a high risk of breast cancer. The current study focused on exploring the relationship between the presence of BRCA1/2 mutations and some clinicopathological characteristics which might impact the pathogenesis of BC disease.

Material and Methods: Genomic DNA samples were obtained from 19 fresh tissues using Gene JET Extraction Kit (Thermo Scientific/US, Canada), and 29 FFPE using QIAamp DNA FFPE Tissue Kit (Qiagen, Valencia, USA) obtained from pretreatment BC patients. Library preparation was performed using Devyser BRCA NGS kit (DEVYSER, Stockholm, Sweden), according to the manufacturer's instructions. The reagent kit V2, 500 Cycles PE, on the Illumina MiSeq System (Illumina, San Diego, CA, USA). The BRCA1 and BRCA2 genes reference were: NM_007300 and NM_000059, respectively. Variants were called using freebayes (1.1.0.46) and annotated using ANNOVAR(version2019Oct24). All samples were subjected for detection of Human Mammary Tumor Virus (HMTV) and Human Papillomavirus (HPV) DNAs using qualitative PCR assay.

Result: The study identified 40 and 54 different BRCA1 and BRCA2 mutations, mostly in the form of frameshift and stop codon mutations. Regarding, BRCA1, 14 pathogenic mutations were detected, exon10 and exon 9 showed to be the most affected exons representing (c.C1612T (25%) and c.C1471T(22.9%), respectively. For BRCA2, only five pathogenic mutations were identified, exon 11 and exon 14 showed to be the most affected exons (cT4001A(6.25%) and c.7231delA(4.16%), respectively. Regarding relation between BRCA1/2 genes mutations and clinicopathological parameters, BRCA1 and BRCA2 carriers were younger than non-carriers though not significant (p=0.440). Regarding the tumor characteristics, BRCA1/2 carriers had large tumor size (p=0.091), high tumor grade compared to non-carriers but without significance (P=0.098). Micro-classifications positivity (60%) was also more frequently among BRCA1/2 carrier than non-carrier (p= 0.082). Regarding detection of HMTV and HPV, BRCA1/2 mutation carriers has a skew towards negative results (P=&lt;0.001 and 0.004, respectively).

Conclusion: Our data suggest that BRCA1/2 mutations might contribute to the pathogenesis among both familial and non-familial Egyptian breast cancer patients, but we need more sample size to confirm the findings. It also identifies the most affected exons in preparation for establishing a diagnostic tool like HRM for genetic counseling, which will help when selecting treatment modalities for BC patients.

STDF Acknowledgment: This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No.22944

Citation Format: Samah A. Loutfy, Nasra F. Abdel Fattah, Ahmed B. Barakat, Omar R. Alfarouk, Tarek M. Hashem, Ahmed M. Osman, Shimaa A. Metwally, Maha A. Abo-Shadi, Amany M. Helal, Shaza A. Habib, Ahmed A. El Sherif, Abdel Wahab El Ghareeb, Mohamed M. Mouneer, Manar M. Moneer, Marwa A. Abdel-Wahed, Mona A. Salem, Asmaa M. M. M. Salama, Fatma S. Hafez, Sara H. Agwa, Hesham Elghazaly, Manal M. El-Mahdy, Mark J. Dunning, Sherif F. El-Khamisy. BRCA1 and BRCA2 mutations and its clinical relevance among egyptian breast cancer women [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 2512.