Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer

Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer

Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in <i>BRCA1</i> are found in about 7–10% of all familial breast cancers and 10% of o...

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Autores principales: Ahmed Bouras, Melanie Leone, Valerie Bonadona, Marine Lebrun, Alain Calender, Nadia Boutry-Kryza
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
hereditary breast and ovarian cancer
next-generation sequencing
<i>BRCA1</i>
<i>Alu</i>Yb8
retrotransposon
Genetics
QH426-470
Acceso en línea:https://doaj.org/article/d8e7fa6451b04f7e9210e28e72100d03
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spelling oai:doaj.org-article:d8e7fa6451b04f7e9210e28e72100d032021-11-25T17:41:23ZIdentification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer10.3390/genes121117362073-4425https://doaj.org/article/d8e7fa6451b04f7e9210e28e72100d032021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1736https://doaj.org/toc/2073-4425Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in <i>BRCA1</i> are found in about 7–10% of all familial breast cancers and 10% of ovarian cancers. <i>Alu</i> elements are the most abundant mobile DNA element in the human genome and are known to affect the human genome by different mechanisms leading to human disease. We report here the detection, by next-generation sequencing (NGS) analysis coupled with a suitable bioinformatics pipeline, of an <i>Alu</i>Yb8 element in exon 14 of the <i>BRCA1</i> gene in a family with HBOC history first classified as BRCA-negative by Sanger sequencing and first NGS analysis. The c.4475_c.4476ins<i>Alu</i>Yb8 mutation impacts splicing and induces the skipping of exon 14. As a result, the produced mRNA contains a premature stop, leading to the production of a short and likely non-functional protein (pAla1453Glyfs*10). Overall, our study allowed us to identify a novel pathogenic variant in <i>BRCA1</i> and showed the importance of bioinformatics tool improvement and versioning.Ahmed BourasMelanie LeoneValerie BonadonaMarine LebrunAlain CalenderNadia Boutry-KryzaMDPI AGarticlehereditary breast and ovarian cancernext-generation sequencing<i>BRCA1</i><i>Alu</i>Yb8retrotransposonGeneticsQH426-470ENGenes, Vol 12, Iss 1736, p 1736 (2021)
institution DOAJ
collection DOAJ
language EN
topic hereditary breast and ovarian cancer
next-generation sequencing
<i>BRCA1</i>
<i>Alu</i>Yb8
retrotransposon
Genetics
QH426-470
spellingShingle hereditary breast and ovarian cancer
next-generation sequencing
<i>BRCA1</i>
<i>Alu</i>Yb8
retrotransposon
Genetics
QH426-470
Ahmed Bouras
Melanie Leone
Valerie Bonadona
Marine Lebrun
Alain Calender
Nadia Boutry-Kryza
Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
description Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant cancer predisposition syndrome characterized by an increased risk of breast and ovarian cancers. Germline pathogenic variants in <i>BRCA1</i> are found in about 7–10% of all familial breast cancers and 10% of ovarian cancers. <i>Alu</i> elements are the most abundant mobile DNA element in the human genome and are known to affect the human genome by different mechanisms leading to human disease. We report here the detection, by next-generation sequencing (NGS) analysis coupled with a suitable bioinformatics pipeline, of an <i>Alu</i>Yb8 element in exon 14 of the <i>BRCA1</i> gene in a family with HBOC history first classified as BRCA-negative by Sanger sequencing and first NGS analysis. The c.4475_c.4476ins<i>Alu</i>Yb8 mutation impacts splicing and induces the skipping of exon 14. As a result, the produced mRNA contains a premature stop, leading to the production of a short and likely non-functional protein (pAla1453Glyfs*10). Overall, our study allowed us to identify a novel pathogenic variant in <i>BRCA1</i> and showed the importance of bioinformatics tool improvement and versioning.
format article
author Ahmed Bouras
Melanie Leone
Valerie Bonadona
Marine Lebrun
Alain Calender
Nadia Boutry-Kryza
author_facet Ahmed Bouras
Melanie Leone
Valerie Bonadona
Marine Lebrun
Alain Calender
Nadia Boutry-Kryza
author_sort Ahmed Bouras
title Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
title_short Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
title_full Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
title_fullStr Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
title_full_unstemmed Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian Cancer
title_sort identification and characterization of new <i>alu</i> element insertion in the <i>brca1</i> exon 14 associated with hereditary breast and ovarian cancer
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/d8e7fa6451b04f7e9210e28e72100d03
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AT valeriebonadona identificationandcharacterizationofnewialuielementinsertionintheibrca1iexon14associatedwithhereditarybreastandovariancancer
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