Du, Chen, Mark, Dorothea, Wappenschmidt, Barbara, Boeckmann, Beatrix, Pabst, Brigitte, Chan, Saki, Cao, Han, Morlot, Susanne, Scholz, Caroline, Auber, Bernd, Rhiem, Kerstin, Schmutzler, Rita, Illig, Thomas, Schlegelberger, Brigitte and Steinemann, Doris (2018). A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families with hereditary breast and ovarian cancer syndrome. Breast Cancer Res. Treat., 172 (3). S. 561 - 570. NEW YORK: SPRINGER. ISSN 1573-7217
Full text not available from this repository.Abstract
PurposeThe purpose of this study is to characterize a novel structural variant, a large duplication involving exons 1-19 of the BRCA1 gene in four independent families, and to provide diagnostically valuable information including the position of the breakpoints as well as clues to its clinical significance.MethodsThe duplication of exons 1-19 of the BRCA1 gene was initially detected by routine laboratory testing including MLPA analysis and next generation sequencing. For detailed characterization we performed array-comparative genome hybridization analysis, fluorescent in situ hybridization, next generation mapping, and long-distance PCR for break-point sequencing.ResultsOur data revealed a tandem duplication on chromosome 17 that encompassed 357kb and included exons 1-19 of the BRCA1 gene and the genes NBR2, NBR1, TMEM106A, LOC100130581, ARL4D, MIR2117 up to parts of the DHX8 gene. This structural variant appeared as a tandem duplication with breakpoints in intron 19 of the BRCA1 gene and in intron 3 of the DHX8 gene (HGVS:chr17(hg19):g.41210776_41568516dup). Segregation analysis indicated that this structural rearrangement is phased in trans with a known pathogenic exon deletion of the BRCA1 gene in one family.ConclusionsThe copy number variation initially recognized as duplication of exon 1-19 of the BRCA1 gene by MLPA analysis is a structural variation with breakpoints in the BRCA1 and DHX8 genes. Although currently to be classified as a variant of unknown significance, our family data indicates that this duplication may be a benign variation or at least of markedly reduced penetrance since it occurs in trans with another known fully pathogenic variant in the BRCA1 gene.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-163524 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1007/s10549-018-4957-x | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Breast Cancer Res. Treat. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 172 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Number: | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 561 - 570 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2018 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | SPRINGER | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | NEW YORK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1573-7217 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/16352 |
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