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Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre
TP53 variant interpretation is still challenging, especially in patients with attenuated Li–Fraumeni syndrome (LFS). We investigated the prevalence of pathogenic/likely pathogenic (P/LP) variants and LFS disease in the Hungarian population of cancer patients. By testing 893 patients with multiplex o...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471726/ https://www.ncbi.nlm.nih.gov/pubmed/37653074 http://dx.doi.org/10.1038/s41598-023-41481-y |
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author | Butz, Henriett Bozsik, Anikó Grolmusz, Vince Szőcs, Erika Papp, János Patócs, Attila |
author_facet | Butz, Henriett Bozsik, Anikó Grolmusz, Vince Szőcs, Erika Papp, János Patócs, Attila |
author_sort | Butz, Henriett |
collection | PubMed |
description | TP53 variant interpretation is still challenging, especially in patients with attenuated Li–Fraumeni syndrome (LFS). We investigated the prevalence of pathogenic/likely pathogenic (P/LP) variants and LFS disease in the Hungarian population of cancer patients. By testing 893 patients with multiplex or familial cancer, we identified and functionally characterized novel splice variants of TP53 helping accurate variant classification. The differences among various semi-automated interpretation platforms without manual curation highlight the importance of focused interpretation as the automatic classification systems do not apply the TP53-specific criteria. The predicted frequency of the TP53 P/LP variants in Hungary is 0.3 per million which most likely underestimates the real prevalence. The higher detection rate of disease-causing variants in patients with attenuated LFS phenotype compared to the control population (OR 12.5; p < 0.0001) may raise the potential benefit of the TP53 genetic testing as part of the hereditary cancer panels of patients with multiple or familial cancer even when they do not meet Chompret criteria. Tumours developed at an earlier age in phenotypic LFS patients compared to the attenuated LFS patients which complicates genetic counselling as currently there are no different recommendations in surveillance protocols for LFS, phenotypic LFS, and attenuated LFS patients. |
format | Online Article Text |
id | pubmed-10471726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104717262023-09-02 Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre Butz, Henriett Bozsik, Anikó Grolmusz, Vince Szőcs, Erika Papp, János Patócs, Attila Sci Rep Article TP53 variant interpretation is still challenging, especially in patients with attenuated Li–Fraumeni syndrome (LFS). We investigated the prevalence of pathogenic/likely pathogenic (P/LP) variants and LFS disease in the Hungarian population of cancer patients. By testing 893 patients with multiplex or familial cancer, we identified and functionally characterized novel splice variants of TP53 helping accurate variant classification. The differences among various semi-automated interpretation platforms without manual curation highlight the importance of focused interpretation as the automatic classification systems do not apply the TP53-specific criteria. The predicted frequency of the TP53 P/LP variants in Hungary is 0.3 per million which most likely underestimates the real prevalence. The higher detection rate of disease-causing variants in patients with attenuated LFS phenotype compared to the control population (OR 12.5; p < 0.0001) may raise the potential benefit of the TP53 genetic testing as part of the hereditary cancer panels of patients with multiple or familial cancer even when they do not meet Chompret criteria. Tumours developed at an earlier age in phenotypic LFS patients compared to the attenuated LFS patients which complicates genetic counselling as currently there are no different recommendations in surveillance protocols for LFS, phenotypic LFS, and attenuated LFS patients. Nature Publishing Group UK 2023-08-31 /pmc/articles/PMC10471726/ /pubmed/37653074 http://dx.doi.org/10.1038/s41598-023-41481-y 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Butz, Henriett Bozsik, Anikó Grolmusz, Vince Szőcs, Erika Papp, János Patócs, Attila Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title | Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title_full | Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title_fullStr | Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title_full_unstemmed | Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title_short | Challenging interpretation of germline TP53 variants based on the experience of a national comprehensive cancer centre |
title_sort | challenging interpretation of germline tp53 variants based on the experience of a national comprehensive cancer centre |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10471726/ https://www.ncbi.nlm.nih.gov/pubmed/37653074 http://dx.doi.org/10.1038/s41598-023-41481-y |
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