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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MDPI AG
2021-10-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/11/1736 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:28:57Z |
| format | Article |
| id | doaj.art-d8e7fa6451b04f7e9210e28e72100d03 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T05:28:57Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-d8e7fa6451b04f7e9210e28e72100d032023-11-22T23:28:02ZengMDPI AGGenes2073-44252021-10-011211173610.3390/genes12111736Identification and Characterization of New <i>Alu</i> Element Insertion in the <i>BRCA1</i> Exon 14 Associated with Hereditary Breast and Ovarian CancerAhmed Bouras0Melanie Leone1Valerie Bonadona2Marine Lebrun3Alain Calender4Nadia Boutry-Kryza5Department of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, 69500 Bron, FranceDepartment of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, 69500 Bron, FranceUnit of Prevention and Genetic Epidemiology, UMR CNRS 5558, Centre Léon Bérard, 69008 Lyon, FranceDepartment of Genetics, Saint Etienne University Hospital, 42270 Saint Priez en Jarez, FranceDepartment of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, 69500 Bron, FranceDepartment of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, 69500 Bron, FranceHereditary 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.https://www.mdpi.com/2073-4425/12/11/1736hereditary breast and ovarian cancernext-generation sequencing<i>BRCA1</i><i>Alu</i>Yb8retrotransposon |
| spellingShingle | 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 Genes hereditary breast and ovarian cancer next-generation sequencing <i>BRCA1</i> <i>Alu</i>Yb8 retrotransposon |
| 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_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_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_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 |
| topic | hereditary breast and ovarian cancer next-generation sequencing <i>BRCA1</i> <i>Alu</i>Yb8 retrotransposon |
| url | https://www.mdpi.com/2073-4425/12/11/1736 |
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