New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman
Background. The identification of the ethnospecific mutations associated with hereditary breast cancer remains challenging. Next generation sequencing (Ngs) technology fully enables the compilation of germline variants associated with the risk for inherited diseases. Despite the success of the Ngs,...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Tomsk National Research Medical Center
2022-01-01
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| Series: | Сибирский онкологический журнал |
| Subjects: | |
| Online Access: | https://www.siboncoj.ru/jour/article/view/2000 |
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| author | P. A. Gervas A. Yu. Molokov A. A. Zarubin A. A. Ponomareva N. N. Babyshkina V. A. Belyavskaya L. F. Pisareva E. L. Choynzonov N. V. Cherdyntseva |
| author_facet | P. A. Gervas A. Yu. Molokov A. A. Zarubin A. A. Ponomareva N. N. Babyshkina V. A. Belyavskaya L. F. Pisareva E. L. Choynzonov N. V. Cherdyntseva |
| author_sort | P. A. Gervas |
| collection | DOAJ |
| description | Background. The identification of the ethnospecific mutations associated with hereditary breast cancer remains challenging. Next generation sequencing (Ngs) technology fully enables the compilation of germline variants associated with the risk for inherited diseases. Despite the success of the Ngs, up to 20 % of molecular tests report genetic variant of unknown significance (Vus) or novel variants that have never been previously described and their clinical significances are unknown. To obtain extended information about the variants of the unknown significance, it is necessary to use an alternative approach for the analysis of the Ngs data. To obtain extended characteristic about the unknown significance variants, it is necessary to search for additional tools for the analysis of the Ngs data. Material and methods. We reclassified the mutation of the unknown significance using the activedrivedb database that assessed the effect of mutations on sites of post-translational modifications, and the proteinpaint tool that complemented the existing cancer genome portals and provided a comprehensive and intuitive view of cancer genomic data. Results. In this study, we report a 44-year-old tuvinian woman with a family history of breast cancer. Based on the Ngs data, mutational analysis revealed the presence of the lrg_321t1: c.80c>t heterozygous variant in exon 2, which led to the proline to leucine change at codon 27 of the protein. In the dbpubmed database, this mutation was determined as unknown significance due to data limitation. According to the data of the activedriverdb tool, this mutation is located distally at the site of post-translational protein modification, which is responsible for binding to kinases that regulate genes of the cell cycle, etc. (atm, chek2, cdk, mapk). In accordance with proteinpaint tool, the lrg_321t1: c.80c>t mutation is located in functionally specialized transactivation domains and codon of the tp53 gene, where the pathogenic mutation associated with li-Fraumeni syndrome has been earlier described. Conclusion. This report is the first to describe a new variant in the tp53 gene (rs1555526933), which is likely to be associated with hereditary cancer-predisposing syndrome, including li-Fraumeni syndrome, in a tuvinian Bc patient with young-onset and familial Bc. |
| first_indexed | 2024-04-10T01:51:49Z |
| format | Article |
| id | doaj.art-1c1195da8e504c0c90378ec055b8c48f |
| institution | Directory Open Access Journal |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| last_indexed | 2024-04-10T01:51:49Z |
| publishDate | 2022-01-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj.art-1c1195da8e504c0c90378ec055b8c48f2023-03-13T09:05:55ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682022-01-0120616417010.21294/1814-4861-2021-20-6-164-170936New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian womanP. A. Gervas0A. Yu. Molokov1A. A. Zarubin2A. A. Ponomareva3N. N. Babyshkina4V. A. Belyavskaya5L. F. Pisareva6E. L. Choynzonov7N. V. Cherdyntseva8Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукНаучно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр, Российская академия наукНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор»Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукBackground. The identification of the ethnospecific mutations associated with hereditary breast cancer remains challenging. Next generation sequencing (Ngs) technology fully enables the compilation of germline variants associated with the risk for inherited diseases. Despite the success of the Ngs, up to 20 % of molecular tests report genetic variant of unknown significance (Vus) or novel variants that have never been previously described and their clinical significances are unknown. To obtain extended information about the variants of the unknown significance, it is necessary to use an alternative approach for the analysis of the Ngs data. To obtain extended characteristic about the unknown significance variants, it is necessary to search for additional tools for the analysis of the Ngs data. Material and methods. We reclassified the mutation of the unknown significance using the activedrivedb database that assessed the effect of mutations on sites of post-translational modifications, and the proteinpaint tool that complemented the existing cancer genome portals and provided a comprehensive and intuitive view of cancer genomic data. Results. In this study, we report a 44-year-old tuvinian woman with a family history of breast cancer. Based on the Ngs data, mutational analysis revealed the presence of the lrg_321t1: c.80c>t heterozygous variant in exon 2, which led to the proline to leucine change at codon 27 of the protein. In the dbpubmed database, this mutation was determined as unknown significance due to data limitation. According to the data of the activedriverdb tool, this mutation is located distally at the site of post-translational protein modification, which is responsible for binding to kinases that regulate genes of the cell cycle, etc. (atm, chek2, cdk, mapk). In accordance with proteinpaint tool, the lrg_321t1: c.80c>t mutation is located in functionally specialized transactivation domains and codon of the tp53 gene, where the pathogenic mutation associated with li-Fraumeni syndrome has been earlier described. Conclusion. This report is the first to describe a new variant in the tp53 gene (rs1555526933), which is likely to be associated with hereditary cancer-predisposing syndrome, including li-Fraumeni syndrome, in a tuvinian Bc patient with young-onset and familial Bc.https://www.siboncoj.ru/jour/article/view/2000наследственные мутации, рак молочной железы, малые народы россии, этносы, тувинцы |
| spellingShingle | P. A. Gervas A. Yu. Molokov A. A. Zarubin A. A. Ponomareva N. N. Babyshkina V. A. Belyavskaya L. F. Pisareva E. L. Choynzonov N. V. Cherdyntseva New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman Сибирский онкологический журнал наследственные мутации, рак молочной железы, малые народы россии, этносы, тувинцы |
| title | New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman |
| title_full | New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman |
| title_fullStr | New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman |
| title_full_unstemmed | New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman |
| title_short | New mutation of the TP53 gene associated with the hereditary breast cancer in a young Tuvinian woman |
| title_sort | new mutation of the tp53 gene associated with the hereditary breast cancer in a young tuvinian woman |
| topic | наследственные мутации, рак молочной железы, малые народы россии, этносы, тувинцы |
| url | https://www.siboncoj.ru/jour/article/view/2000 |
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