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

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Abstract

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.

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Data availability

The data (including patient demographic information and mutations) and the code of the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Medical Genetics, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey

    Ibrahim Sahin & Hanife Saat

Authors
  1. Ibrahim Sahin
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  2. Hanife Saat
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Contributions

IS designed the research, analyzed and interpreted the results (including the coding part with Python version 3.9.2), wrote the manuscript, and approved the final manuscript. HS collected the data, analyzed and interpreted the results, reviewed the manuscript, and approved the final manuscript.

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Correspondence to Ibrahim Sahin.

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The authors declare that there is no conflict of interest.

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We confirm that we have read the journal’s position on issues involved in the ethical publication, and we affirm that this report is consistent with those guidelines. The Ethics Committee of the University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital approved the study (08.03.2021-106/27).

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Sahin, I., Saat, H. A novel BRCA1 duplication and new insights on the spectrum and frequency of germline large genomic rearrangements in BRCA1/BRCA2. Mol Biol Rep 48, 5057–5062 (2021). https://doi.org/10.1007/s11033-021-06499-3

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  • DOI: https://doi.org/10.1007/s11033-021-06499-3

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