A novel BRCA1 duplication and new insights on the spectrum and frequency of germline large genomic rearrangements in BRCA1/BRCA2

• Published in: Molecular biology reports 2021-06, Vol.48 (6), p.5057-5062
• Main Authors: Sahin, Ibrahim, Saat, Hanife
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; BRCA1 protein; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; BRCA2 protein; BRCA2 Protein - genetics; BRCA2 Protein - metabolism; Breast cancer; Breast Neoplasms - genetics; Carcinogenesis; Exons - genetics; Female; Gene Deletion; Gene duplication; Gene Duplication - genetics; Gene Rearrangement - genetics; Genes, BRCA1 - physiology; Genes, BRCA2 - physiology; Genetic disorders; Genetic Predisposition to Disease - genetics; Genetic screening; Genetic Testing - methods; Genomics; Genomics - methods; Germ Cells - metabolism; Germ-Line Mutation - genetics; Histology; Humans; Life Sciences; Morphology; Mutation; Mutation - genetics; Neoplasm Recurrence, Local - genetics; Next-generation sequencing; Original Article; Ovarian cancer; Ovarian Neoplasms - genetics; Patients; Turkey
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06499-3

Heritable breast cancers account for 5% to 10% of all breast cancers, and monogenic, highly penetrant genes cause them. Around 90% of pathogenic variants in BRCA1 and BRCA2 are observed using gene sequencing, with another 10% identified through gene duplication/deletion analysis, which differs across various communities. In this study, we performed a next-generation sequencing panel and MLPA on 1484 patients to explain the importance of recurrent germline duplications/deletions of BRCA1-2 and their clinical results and determine how often BRCA gene LGRs were seen in people suspected of hereditary breast and ovarian cancer syndrome. The large genomic rearrangements (LGRs) frequency was approximately 1% (14/1484). All 14 mutations were heterozygous and detected in patients with breast cancer. BRCA1 mutations were more predominant ( n  = 8, 57.1%) than BRCA2 mutations (6, 42.9%). The most common recurrent mutations were BRCA2 exon three and BRCA1 exon 24 (23) deletions. To the best of our knowledge, BRCA1 5’UTR-exon11 duplication has never been reported before. Testing with MLPA is essential to identify patients at high risk. Our data demonstrate that BRCA1-2 LGRs should be considered when ordering genetic testing for individuals with a personal or family history of cancer, particularly breast cancer. Further research could shed light on BRCA1-2 LGRs’ unique carcinogenesis roles.