Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach
BackgroundHereditary cancer predisposition syndromes account for approximately 10% of cancer cases. Next generation sequencing (NGS) based multi-gene targeted panels is now a frontline approach to identify pathogenic mutations in cancer predisposition genes in high-risk families. Recent evolvement o...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.698595/full |
| _version_ | 1818738111463555072 |
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| author | Pratibha Bhai Michael A. Levy Kathleen Rooney Deanna Alexis Carere Jack Reilly Jennifer Kerkhof Michael Volodarsky Alan Stuart Mike Kadour Mike Kadour Karen Panabaker Laila C. Schenkel Laila C. Schenkel Hanxin Lin Hanxin Lin Peter Ainsworth Peter Ainsworth Peter Ainsworth Bekim Sadikovic Bekim Sadikovic |
| author_facet | Pratibha Bhai Michael A. Levy Kathleen Rooney Deanna Alexis Carere Jack Reilly Jennifer Kerkhof Michael Volodarsky Alan Stuart Mike Kadour Mike Kadour Karen Panabaker Laila C. Schenkel Laila C. Schenkel Hanxin Lin Hanxin Lin Peter Ainsworth Peter Ainsworth Peter Ainsworth Bekim Sadikovic Bekim Sadikovic |
| author_sort | Pratibha Bhai |
| collection | DOAJ |
| description | BackgroundHereditary cancer predisposition syndromes account for approximately 10% of cancer cases. Next generation sequencing (NGS) based multi-gene targeted panels is now a frontline approach to identify pathogenic mutations in cancer predisposition genes in high-risk families. Recent evolvement of NGS technologies have allowed simultaneous detection of sequence and copy number variants (CNVs) using a single platform. In this study, we have analyzed frequency and nature of sequence variants and CNVs, in a Canadian cohort of patients, suspected with hereditary cancer syndrome, referred for genetic testing following specific genetic testing guidelines based on patient’s personal and/or family history of cancer.MethodsA 2870 patients were subjected to a single NGS based multi-gene targeted hereditary cancer panel testing algorithm to identify sequence variants and CNVs in cancer predisposition genes at our reference laboratory in Southwestern Ontario. CNVs identified by NGS were confirmed by alternative techniques like Multiplex ligation-dependent probe amplification (MLPA).ResultsA 15% (431/2870) patients had a pathogenic variant and 36% (1032/2870) had a variant of unknown significance (VUS), in a cancer susceptibility gene. A total of 287 unique pathogenic variant were identified, out of which 23 (8%) were novel. CNVs identified by NGS based approach accounted for 9.5% (27/287) of pathogenic variants, confirmed by alternate techniques with high accuracy.ConclusionThis study emphasizes the utility of NGS based targeted testing approach to identify both sequence and CNVs in patients suspected with hereditary cancer syndromes in clinical setting and expands the mutational spectrum of high and moderate penetrance cancer predisposition genes. |
| first_indexed | 2024-12-18T01:03:45Z |
| format | Article |
| id | doaj.art-22fc06b1488549319e08328937c5ba16 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-18T01:03:45Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-22fc06b1488549319e08328937c5ba162022-12-21T21:26:18ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-07-011210.3389/fgene.2021.698595698595Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based ApproachPratibha Bhai0Michael A. Levy1Kathleen Rooney2Deanna Alexis Carere3Jack Reilly4Jennifer Kerkhof5Michael Volodarsky6Alan Stuart7Mike Kadour8Mike Kadour9Karen Panabaker10Laila C. Schenkel11Laila C. Schenkel12Hanxin Lin13Hanxin Lin14Peter Ainsworth15Peter Ainsworth16Peter Ainsworth17Bekim Sadikovic18Bekim Sadikovic19Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, CanadaMedical Genetics Program of Southwestern Ontario, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, London Health Sciences Centre, London, ON, CanadaMolecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON, CanadaBackgroundHereditary cancer predisposition syndromes account for approximately 10% of cancer cases. Next generation sequencing (NGS) based multi-gene targeted panels is now a frontline approach to identify pathogenic mutations in cancer predisposition genes in high-risk families. Recent evolvement of NGS technologies have allowed simultaneous detection of sequence and copy number variants (CNVs) using a single platform. In this study, we have analyzed frequency and nature of sequence variants and CNVs, in a Canadian cohort of patients, suspected with hereditary cancer syndrome, referred for genetic testing following specific genetic testing guidelines based on patient’s personal and/or family history of cancer.MethodsA 2870 patients were subjected to a single NGS based multi-gene targeted hereditary cancer panel testing algorithm to identify sequence variants and CNVs in cancer predisposition genes at our reference laboratory in Southwestern Ontario. CNVs identified by NGS were confirmed by alternative techniques like Multiplex ligation-dependent probe amplification (MLPA).ResultsA 15% (431/2870) patients had a pathogenic variant and 36% (1032/2870) had a variant of unknown significance (VUS), in a cancer susceptibility gene. A total of 287 unique pathogenic variant were identified, out of which 23 (8%) were novel. CNVs identified by NGS based approach accounted for 9.5% (27/287) of pathogenic variants, confirmed by alternate techniques with high accuracy.ConclusionThis study emphasizes the utility of NGS based targeted testing approach to identify both sequence and CNVs in patients suspected with hereditary cancer syndromes in clinical setting and expands the mutational spectrum of high and moderate penetrance cancer predisposition genes.https://www.frontiersin.org/articles/10.3389/fgene.2021.698595/fullnext generation sequencingcopy number variantsfamilial cancer syndromesbreast cancercolorectal cancer |
| spellingShingle | Pratibha Bhai Michael A. Levy Kathleen Rooney Deanna Alexis Carere Jack Reilly Jennifer Kerkhof Michael Volodarsky Alan Stuart Mike Kadour Mike Kadour Karen Panabaker Laila C. Schenkel Laila C. Schenkel Hanxin Lin Hanxin Lin Peter Ainsworth Peter Ainsworth Peter Ainsworth Bekim Sadikovic Bekim Sadikovic Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach Frontiers in Genetics next generation sequencing copy number variants familial cancer syndromes breast cancer colorectal cancer |
| title | Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach |
| title_full | Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach |
| title_fullStr | Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach |
| title_full_unstemmed | Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach |
| title_short | Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach |
| title_sort | analysis of sequence and copy number variants in canadian patient cohort with familial cancer syndromes using a unique next generation sequencing based approach |
| topic | next generation sequencing copy number variants familial cancer syndromes breast cancer colorectal cancer |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.698595/full |
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