Document Type : Research Articles
Authors
1
Biochemistry Department, Biotechnology Research Institute, Giza, Egypt.
2
High Throughput Molecular and Genetic laboratory, Central Laboratories Network and the Centers of Excellence, National Research Centre, Dokki, Giza, Egypt.
3
CSO at Omicsense, Cairo, Egypt.
4
Molecular pathology lab Children Cancer Hospital 57357, Cairo, Egypt.
5
Zoology Department, Faculty of Science, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt.
6
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
7
Department of Medical Laboratory Technology, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia.
8
Medical Oncology Department, National Cancer Institute, Cairo, Egypt.
Abstract
Background: Breast cancer is the most common cancer affecting females according to WHO 2020 report, with BRCA1 and BRCA2 identified as the major tumor suppressor genes linked to disease susceptibility. Hence, the purpose of the current study was to investigate germline mutations among these genes in a group of Egyptian female breast cancer patients. Methods: Blood samples from primary breast cancer patients (n=22), benign breast lesions (n=5) and healthy controls (n=7) were sequenced for BRCA genes by next generation sequencer. Results: A total of 135 genetic variations were detected, 59 in BRCA1 and 76 BRCA2, 2 indels (insertion-deletion) and 133 SNV (single nucleotide variation), nearly 55% of those variants were missense variants, 38% were synonymous and 7% were nonsense. A total of 59 variations were detected in BRCA1 and they were categorized as exonic (n=10) and intronic (n=49) regions, BRCA1 exonic variants were categorized into: missense (n=12), non-coding transcript (n=11) synonymous (n=6), splice region synonymous (n=2), stop gain (n=2) and 3-prime UTR (n=1) variants. Regarding variations detected in BRCA2, 55 intronic and 21 exonic variants were identified. Among these 21 variants; 13 novel mutations and 8 formally reported as follows: 7 as benign and one previously reported with contradictory pathogenicity according to the Clinvar database which is a freely available, public archive of reports of the relationships between human variations and phenotypes hosted by the National Center for Biotechnology Information (NCBI) and funded by intramural National Institutes of Health (NIH) funding. Conclusion: BRCA1 and BRCA2 germline profiling based on next-generation sequencing technology among Egyptian breast cancer female patients revealed 135 germline variations -104 intronic and 31 exonic, respectively. Among the exonic variants; 13 were newly reported mutations. Hence further study is required to enhance mutational analysis which may benefit clinical system.
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