Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.

Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patien...

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Autores principales:	Felipe Vaca-Paniagua, Rosa María Alvarez-Gomez, Verónica Fragoso-Ontiveros, Silvia Vidal-Millan, Luis Alonso Herrera, David Cantú, Enrique Bargallo-Rocha, Alejandro Mohar, César López-Camarillo, Carlos Pérez-Plasencia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c5d0369768842878eb1296cfc2a54a6
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spelling	oai:doaj.org-article:2c5d0369768842878eb1296cfc2a54a62021-11-18T07:17:33ZFull-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.1932-620310.1371/journal.pone.0037432https://doaj.org/article/2c5d0369768842878eb1296cfc2a54a62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22655046/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41-485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing.Felipe Vaca-PaniaguaRosa María Alvarez-GomezVerónica Fragoso-OntiverosSilvia Vidal-MillanLuis Alonso HerreraDavid CantúEnrique Bargallo-RochaAlejandro MoharCésar López-CamarilloCarlos Pérez-PlasenciaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37432 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felipe Vaca-Paniagua Rosa María Alvarez-Gomez Verónica Fragoso-Ontiveros Silvia Vidal-Millan Luis Alonso Herrera David Cantú Enrique Bargallo-Rocha Alejandro Mohar César López-Camarillo Carlos Pérez-Plasencia Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
description	Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41-485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing.
format	article
author	Felipe Vaca-Paniagua Rosa María Alvarez-Gomez Verónica Fragoso-Ontiveros Silvia Vidal-Millan Luis Alonso Herrera David Cantú Enrique Bargallo-Rocha Alejandro Mohar César López-Camarillo Carlos Pérez-Plasencia
author_facet	Felipe Vaca-Paniagua Rosa María Alvarez-Gomez Verónica Fragoso-Ontiveros Silvia Vidal-Millan Luis Alonso Herrera David Cantú Enrique Bargallo-Rocha Alejandro Mohar César López-Camarillo Carlos Pérez-Plasencia
author_sort	Felipe Vaca-Paniagua
title	Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
title_short	Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
title_full	Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
title_fullStr	Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
title_full_unstemmed	Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.
title_sort	full-exon pyrosequencing screening of brca germline mutations in mexican women with inherited breast and ovarian cancer.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2c5d0369768842878eb1296cfc2a54a6
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Full-exon pyrosequencing screening of BRCA germline mutations in Mexican women with inherited breast and ovarian cancer.

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