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Open AccessArticle

Complex Characterization of Germline Large Genomic Rearrangements of the BRCA1 and BRCA2 Genes in High-Risk Breast Cancer Patients—Novel Variants from a Large National Center

by 1,2,*,†, 1,†, 1,2, 1,‡, 1,2,3, 1,2,3 and 1
1
Department of Molecular Genetics, National Institute of Oncology, Ráth György utca 7-9, H-1122 Budapest, Hungary
2
Hereditary Cancers Research Group, Nagyvárad tér 4, H-1089 Budapest, Hungary
3
Department of Laboratory Medicine, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
This author’s present affiliation: Department of Pathogenetics, National Institute of Oncology, Ráth György utca 7-9, H-1122 Budapest, Hungary.
Int. J. Mol. Sci. 2020, 21(13), 4650; https://doi.org/10.3390/ijms21134650
Received: 20 May 2020 / Revised: 19 June 2020 / Accepted: 27 June 2020 / Published: 30 June 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Large genomic rearrangements (LGRs) affecting one or more exons of BRCA1 and BRCA2 constitute a significant part of the mutation spectrum of these genes. Since 2004, the National Institute of Oncology, Hungary, has been involved in screening for LGRs of breast or ovarian cancer families enrolled for genetic testing. LGRs were detected by multiplex ligation probe amplification method, or next-generation sequencing. Where it was possible, transcript-level characterization of LGRs was performed. Phenotype data were collected and analyzed too. Altogether 28 different types of LGRs in 51 probands were detected. Sixteen LGRs were novel. Forty-nine cases were deletions or duplications in BRCA1 and two affected BRCA2. Rearrangements accounted for 10% of the BRCA1 mutations. Three exon copy gains, two complex rearrangements, and 23 exon losses were characterized by exact breakpoint determinations. The inferred mechanisms for LGR formation were mainly end-joining repairs utilizing short direct homologies. Comparing phenotype features of the LGR-carriers to that of the non-LGR BRCA1 mutation carriers, revealed no significant differences. Our study is the largest comprehensive report of LGRs of BRCA1/2 in familial breast and ovarian cancer patients in the Middle and Eastern European region. Our data add novel insights to genetic interpretation associated to the LGRs. View Full-Text
Keywords: BRCA1; BRCA2; large genomic rearrangement; familial breast cancer; copy number analysis; breakpoint characterization; deletion; duplication BRCA1; BRCA2; large genomic rearrangement; familial breast cancer; copy number analysis; breakpoint characterization; deletion; duplication
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MDPI and ACS Style

Bozsik, A.; Pócza, T.; Papp, J.; Vaszkó, T.; Butz, H.; Patócs, A.; Oláh, E. Complex Characterization of Germline Large Genomic Rearrangements of the BRCA1 and BRCA2 Genes in High-Risk Breast Cancer Patients—Novel Variants from a Large National Center. Int. J. Mol. Sci. 2020, 21, 4650. https://doi.org/10.3390/ijms21134650

AMA Style

Bozsik A, Pócza T, Papp J, Vaszkó T, Butz H, Patócs A, Oláh E. Complex Characterization of Germline Large Genomic Rearrangements of the BRCA1 and BRCA2 Genes in High-Risk Breast Cancer Patients—Novel Variants from a Large National Center. International Journal of Molecular Sciences. 2020; 21(13):4650. https://doi.org/10.3390/ijms21134650

Chicago/Turabian Style

Bozsik, Anikó; Pócza, Tímea; Papp, János; Vaszkó, Tibor; Butz, Henriett; Patócs, Attila; Oláh, Edit. 2020. "Complex Characterization of Germline Large Genomic Rearrangements of the BRCA1 and BRCA2 Genes in High-Risk Breast Cancer Patients—Novel Variants from a Large National Center" Int. J. Mol. Sci. 21, no. 13: 4650. https://doi.org/10.3390/ijms21134650

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