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Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients
Here we report the results of a retrospective germline analysis of 6941 individuals fulfilling the criteria necessary for genetic testing of hereditary breast- and ovarian cancer (HBOC) according to the German S3 or AGO Guidelines. Genetic testing was performed by next-generation sequencing using 12...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400578/ https://www.ncbi.nlm.nih.gov/pubmed/37188824 http://dx.doi.org/10.1038/s41431-023-01380-2 |
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author | Henkel, Jan Laner, Andreas Locher, Melanie Wohlfrom, Tobias Neitzel, Birgit Becker, Kerstin Neuhann, Teresa Abicht, Angela Steinke-Lange, Verena Holinski-Feder, Elke |
author_facet | Henkel, Jan Laner, Andreas Locher, Melanie Wohlfrom, Tobias Neitzel, Birgit Becker, Kerstin Neuhann, Teresa Abicht, Angela Steinke-Lange, Verena Holinski-Feder, Elke |
author_sort | Henkel, Jan |
collection | PubMed |
description | Here we report the results of a retrospective germline analysis of 6941 individuals fulfilling the criteria necessary for genetic testing of hereditary breast- and ovarian cancer (HBOC) according to the German S3 or AGO Guidelines. Genetic testing was performed by next-generation sequencing using 123 cancer-associated genes based on the Illumina TruSight® Cancer Sequencing Panel. In 1431 of 6941 cases (20.6%) at least one variant was reported (ACMG/AMP classes 3–5). Of those 56.3% (n = 806) were class 4 or 5 and 43.7% (n = 625) were a class 3 (VUS). We defined a 14 gene HBOC core gene panel and compared this to a national and different internationally recommended gene panels (German Hereditary Breast and Ovarian Cancer Consortium HBOC Consortium, ClinGen expert Panel, Genomics England PanelsApp) in regard of diagnostic yield, revealing a diagnostic range of pathogenic variants (class 4/5) from 7.8 to 11.6% depending on the panel evaluated. With the 14 HBOC core gene panel having a diagnostic yield of pathogenic variants (class 4/5) of 10.8%. Additionally, 66 (1%) pathogenic variants (ACMG/AMP class 4 or 5) were found in genes outside the 14 HBOC core gene set (secondary findings) that would have been missed with the restriction to the analysis of HBOC genes. Furthermore, we evaluated a workflow for a periodic re-evaluation of variants of uncertain clinical significance (VUS) for the improvement of clinical validity of germline genetic testing. |
format | Online Article Text |
id | pubmed-10400578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-104005782023-08-05 Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients Henkel, Jan Laner, Andreas Locher, Melanie Wohlfrom, Tobias Neitzel, Birgit Becker, Kerstin Neuhann, Teresa Abicht, Angela Steinke-Lange, Verena Holinski-Feder, Elke Eur J Hum Genet Article Here we report the results of a retrospective germline analysis of 6941 individuals fulfilling the criteria necessary for genetic testing of hereditary breast- and ovarian cancer (HBOC) according to the German S3 or AGO Guidelines. Genetic testing was performed by next-generation sequencing using 123 cancer-associated genes based on the Illumina TruSight® Cancer Sequencing Panel. In 1431 of 6941 cases (20.6%) at least one variant was reported (ACMG/AMP classes 3–5). Of those 56.3% (n = 806) were class 4 or 5 and 43.7% (n = 625) were a class 3 (VUS). We defined a 14 gene HBOC core gene panel and compared this to a national and different internationally recommended gene panels (German Hereditary Breast and Ovarian Cancer Consortium HBOC Consortium, ClinGen expert Panel, Genomics England PanelsApp) in regard of diagnostic yield, revealing a diagnostic range of pathogenic variants (class 4/5) from 7.8 to 11.6% depending on the panel evaluated. With the 14 HBOC core gene panel having a diagnostic yield of pathogenic variants (class 4/5) of 10.8%. Additionally, 66 (1%) pathogenic variants (ACMG/AMP class 4 or 5) were found in genes outside the 14 HBOC core gene set (secondary findings) that would have been missed with the restriction to the analysis of HBOC genes. Furthermore, we evaluated a workflow for a periodic re-evaluation of variants of uncertain clinical significance (VUS) for the improvement of clinical validity of germline genetic testing. Springer International Publishing 2023-05-15 2023-08 /pmc/articles/PMC10400578/ /pubmed/37188824 http://dx.doi.org/10.1038/s41431-023-01380-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Henkel, Jan Laner, Andreas Locher, Melanie Wohlfrom, Tobias Neitzel, Birgit Becker, Kerstin Neuhann, Teresa Abicht, Angela Steinke-Lange, Verena Holinski-Feder, Elke Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title | Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title_full | Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title_fullStr | Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title_full_unstemmed | Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title_short | Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients |
title_sort | diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected hboc patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400578/ https://www.ncbi.nlm.nih.gov/pubmed/37188824 http://dx.doi.org/10.1038/s41431-023-01380-2 |
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