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Newly identified molecular and genetic characteristics of primary mediastinal large B-cell lymphomaстатья
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: Kamaeva Inna A., Novikova Inna A., Lysenko Irina B., Timoshkina Natalya N., Nikolaeva Nadezhda V., Kapuza Elena A., Gaysultanova Yakha S., Pushkareva Tatiana F., Tishina Anna V., Samaneva Natalia Yu, Vladimirova Liubov Yu
- Журнал: Journal of Clinical Oncology
- Том: 40
- Номер: 16_suppl
- Год издания: 2022
- Издательство: American Society of Clinical Oncology
- Местоположение издательства: United States
- Первая страница: e19580
- Последняя страница: e19580
- DOI: 10.1200/jco.2022.40.16_suppl.e19580
- Аннотация: Background: Many studies have been devoted to the molecular profile of diffuse large B-cell lymphoma; however, a clear molecular and genetic picture of primary mediastinal large B-cell lymphoma (PMBLC) has not yet been described. Studies have reported various signaling pathways involved in PMBCL pathogenesis, with the best known JAK-STAT and NF-kB. This study was aimed at the detection of previously undescribed mutations, as well as the identification of signaling pathways that may be of interest in the search for new therapeutic targets for PMBCL. Methods: Tumor biopsy specimens from 23 PMBCL patients were examined by next-generation sequencing (NGS) on the Illumina NextSeq 550 system with an average coverage of at least 100x using the AVENIO Tumor Expanded Panel (Roche, USA) containing 77 genes. Analytical sensitivity of mutation detection was 5%. The pathogenicity of the identified nucleotide substitutions was assessed according to ACMG (American College of Medical Genetics and Genomics) and AMP (Association of Molecular Pathology) recommendations. Genomic DNAs were extracted from FFPE blocks using the Gene Read DNA FFPE Kit panel (Qiagen, USA) according to the standard protocol. DNA concentrations were measured fluorimetrically on the Qubit 2.0 fluorometer (Life Technologies, USA). The AVENIO Oncology Analysis Software was used to process the data and to search for clinically significant mutations. The genetic material was analyzed for clinically significant mutations among well-known databases: COSMIC: V83, TCGA 9.0, Exac: 1.0, DBSNP: 150, 1000 Genomes: phase_3_v5b, Snpeff: 4.2. Results: The targeted high-performance sequencing of PMBLC samples showed a newly revealed range of polymorphisms in 9 genes in patients with PMBLC (Alk, TP53, CCND3, RNF43, PIK3CA, FGFR3, SMO, MET, EZH2), previously not described for this cancer. We also interpreted signal pathways related to the mutated genes. Conclusions: The identified polymorphisms and the relationship of mutated genes with PMBLC signaling paths can serve as new therapeutic targets for patients with PMBLC.
- Добавил в систему: Владимирова Любовь Юрьевна