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High frequency of c-KIT genetic variants in exons 9, 11, 13 and 17 and PDGFRA in exon 18 in gastric GIST tumorsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или ScopusДата последнего поиска статьи во внешних источниках: 20 июня 2024 г.
- Авторы: Omelchuk Ekaterina P., Gvaldin Dmitry Yu, Timoshkina Natalya N., Vladimirova Liubov Yu, Gevorkyan Yuriy A., Soldatkina Natalya V., Kharagezov Dmitry A., Dashkov Andrey V., Kaymakchi Dmitry O., Poluektov Sergey I., Kolesnikov Vladimir E., Dontsov Vladimir A., Tolmakh Roman E., Ilchenko Sergei A., Stateshny Oleg N., Petrov Dmitry S., Grechkin Fedor N., Oganyan Nairi B., Kolesnikov Valeriy V., Mirzoyan Ellada
- Журнал: Journal of Clinical Oncology
- Том: 38
- Номер: 15_suppl
- Год издания: 2020
- Издательство: American Society of Clinical Oncology
- Местоположение издательства: United States
- Первая страница: e23525
- Последняя страница: e23525
- DOI: 10.1200/jco.2020.38.15_suppl.e23525
- Аннотация: Background: Gastrointestinal stromal tumors (GIST) are rare malignant mesenchymal neoplasms of the gastrointestinal tract, the diagnosis and treatment of which is associated with the presence of mutations in the c-KIT and PDGFRA genes. Purpose of this study was molecular genetic genotyping of GIST according to clinically significant exons of the c-KIT and PDGFRA genes. Methods: The study included patients with an immunohistochemically confirmed diagnosis of GIST who underwent treatment in the RRIO, Rostov-on-Don, for the period 2018-2019 (n = 20, median age 63.5 years, men/women–10 people each, gastric tumors). DNA was isolated from FFPE tissue using the GeneJET FFPE DNA Purification Kit, USA. The presence of mutations in exons 9, 11, 13 and 17 of c-KIT and exon 18 of PDGFRA was detected by Sanger sequencing. Results: Activating mutations in exon c-KIT were detected in 10 ps, including one substitution p.V560E and 4 deletions – p.V559_E561del, p.M552_V555delMYEV, p.W557_V559 > F and p.W557_V559 > C. These mutations cause sensitivity to imatinib. Pathogenic mutations were detected in PDGFRA exon 18: an activating deletion p.I843_D846delIMHD (2 ps) and a substitution p.D842Y, which determines imatinib resistance (2 ps). Thus, 20% of GIST cases are promising for obtaining avapritinib, the first FDA approved drug in 2020 for patients with GIST with a mutation in PDGFRA exon 18. In addition, neutral genetic variants were revealed: in 17 exon c-KIT in 16 patients, benign rs1008658, in PDGFRA 18 exon – rs3830355 (3 ps) and silent mutation p.V824V (3 ps). Conclusions: Genotyping of c-KIT and PDGFRA identified 12 types of clinically significant mutations and, in 80% of cases, the carriage of benign polymorphisms and / or SNPs of unknown clinical significance. As a result, 70% of patients from the South of Russia with GIST may be sensitive to treatment with imatinib and/or avapritinib.
- Добавил в систему: Владимирова Любовь Юрьевна