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01-08-2010 | Preclinical study

Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes

Authors: Jesús del Valle, Lídia Feliubadaló, Marga Nadal, Alex Teulé, Rosa Miró, Raquel Cuesta, Eva Tornero, Mireia Menéndez, Esther Darder, Joan Brunet, Gabriel Capellà, Ignacio Blanco, Conxi Lázaro

Published in: Breast Cancer Research and Treatment | Issue 3/2010

Abstract

Large genomic rearrangements are estimated to account for approximately 5–10% of all disease-causing mutations in BRCA1 and BRCA2 genes in patients with hereditary breast and ovarian cancer syndrome (HBOC). We use MRC-Holland Multiplex Ligation-dependent Probe Amplification (MLPA) to screen for such rearrangements in patients with HBOC and as a first step in our genetic testing workflow. The technique was applied to a set of 310 independent patients and detected eight different copy number alterations, corresponding to 2.6% of the studied samples. MLPA was also found to identify point mutations located in probe sequences. As commercial MLPA tests are not suitable for determining the specific breakpoints or for defining the exact extent of rearrangements, we applied a set of different complementary techniques to characterize these genetic alterations with greater precision. Long-range PCR amplification, RNA analysis, SNP-array chips, non-commercial MLPA probes, and FISH analysis were used to fully define the extent and mechanism of each alteration. In BRCA1, six rearrangements were characterized: deletion of E22, duplication of E9–E24, deletion of E16–E23, deletion of E1–E13, deletion of E1–E2 and duplication of E1–E2. In BRCA2, we studied a deletion of E15–E16 and a deletion of E1–E24. To the best of our knowledge, this is the most comprehensive study of the nature and underlying molecular causes of these mutational events in the BRCA1/2 genes.

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Title: Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes
Authors: Jesús del Valle
Lídia Feliubadaló
Marga Nadal
Alex Teulé
Rosa Miró
Raquel Cuesta
Eva Tornero
Mireia Menéndez
Esther Darder
Joan Brunet
Gabriel Capellà
Ignacio Blanco
Conxi Lázaro
Publication date: 01-08-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0613-9

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