Investigation of BRCA1 exon 11 genetic variations in breast cancer among Libyan women

Abstract

Introduction The majority of hereditary breast and ovarian cancers are associated with mutations in two genes, breast cancer type 1 and 2 susceptibility genes (BRCA1 and BRCA2). Here, we describe for the first time analysis of BRCA1 exon 11 in 48 Libyan breast cancer patients with a family history of cancer. Methods All patients had a family history of cancer and were included in the study only if they have a family history of breast or ovarian cancer, male breast cancer, or triple negative tumors. PCR was performed using specific primer pairs spanning BRCA1 exon 11 followed by Sanger sequencing. Genetic analysis was done using Sequencher 5.1. Results We identified 12 genetic variants in BRCA1 exon 11. Three variants were novel (c.1019T>C, c.2363T>G, and c.3192T>C). c.2363T>G was predicted by SIFT as damaging. Six variants were of unknown significance (c.918T>C, c.1853G>C, c.1886G>A, c.2215A>G, c.2612C>T, c.3113A>C and c.3784T>C), and 3 were classified as benign in ClinVar database (c.918T>C, c.2082C>T and c.2311T>C). Conclusions Scanning of the entire BRCA1 is needed to identify any associated deleterious mutations. Although the clinical importance of unclassified variants is unknown, the association of certain variants with deleterious mutations and contralateral breast cancer warrants genetic testing and counseling in the Libyan population.

Assessing the Impact of Novel BRCA1 Exon 11 Variants on Pre-mRNA Splicing

“…Sequencing of the BRCA1 gene within a cohort of patients with a family history of cancer revealed the presence of three novel variants (Table 1) previously unreported in studies conducted in Arab countries [16].…”

“…The three novel VUS characterized in this study (Table 1) were identified during a genetic screening carried out in the Oncology Departments of the main public hospitals in Tripoli (Tripoli Central Hospital and Tripoli Medical Center). Complete clinical information on the analyzed patients is reported in a MedRxiv preprint [16]. The table shows the type of variation (missense/synonymous); the resulting amino acid change; and the GenBank identification number as described in a recent preprint [16].…”

“…Complete clinical information on the analyzed patients is reported in a MedRxiv preprint [16]. The table shows the type of variation (missense/synonymous); the resulting amino acid change; and the GenBank identification number as described in a recent preprint [16].…”