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Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report

The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with e...

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Autores principales: Nunziato, Marcella, Starnone, Flavio, Lombardo, Barbara, Pensabene, Matilde, Condello, Caterina, Verdesca, Francesco, Carlomagno, Chiara, De Placido, Sabino, Pastore, Lucio, Salvatore, Francesco, D’Argenio, Valeria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713453/
https://www.ncbi.nlm.nih.gov/pubmed/29165356
http://dx.doi.org/10.3390/ijms18112487
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author Nunziato, Marcella
Starnone, Flavio
Lombardo, Barbara
Pensabene, Matilde
Condello, Caterina
Verdesca, Francesco
Carlomagno, Chiara
De Placido, Sabino
Pastore, Lucio
Salvatore, Francesco
D’Argenio, Valeria
author_facet Nunziato, Marcella
Starnone, Flavio
Lombardo, Barbara
Pensabene, Matilde
Condello, Caterina
Verdesca, Francesco
Carlomagno, Chiara
De Placido, Sabino
Pastore, Lucio
Salvatore, Francesco
D’Argenio, Valeria
author_sort Nunziato, Marcella
collection PubMed
description The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations.
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spelling pubmed-57134532017-12-07 Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report Nunziato, Marcella Starnone, Flavio Lombardo, Barbara Pensabene, Matilde Condello, Caterina Verdesca, Francesco Carlomagno, Chiara De Placido, Sabino Pastore, Lucio Salvatore, Francesco D’Argenio, Valeria Int J Mol Sci Case Report The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4–26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations. MDPI 2017-11-22 /pmc/articles/PMC5713453/ /pubmed/29165356 http://dx.doi.org/10.3390/ijms18112487 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Nunziato, Marcella
Starnone, Flavio
Lombardo, Barbara
Pensabene, Matilde
Condello, Caterina
Verdesca, Francesco
Carlomagno, Chiara
De Placido, Sabino
Pastore, Lucio
Salvatore, Francesco
D’Argenio, Valeria
Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title_full Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title_fullStr Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title_full_unstemmed Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title_short Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report
title_sort fast detection of a brca2 large genomic duplication by next generation sequencing as a single procedure: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713453/
https://www.ncbi.nlm.nih.gov/pubmed/29165356
http://dx.doi.org/10.3390/ijms18112487
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