Study of the mutational profile of a tumor for the selection of targeted therapy

Abstract

Relevance. Currently, the treatment of cancer patients is based on personalized selection of drugs depending on the mutational status of the tumor, which is aimed at clarifying the prognosis of the disease and predicting the response to treatment. Objective of the study. To search for mutations in paraffin-fixed tumor tissues in order to optimize the appointment of targeted therapy. Materials and methods of the study. The study material was paraffin blocks with biopsy/surgical material of patients. DNA and RNA were extracted using the RecoverAll™ Multi-Sample RNA/DNA kit (Termofisher Scientific, USA) in accordance with the manufacturer's instructions. The molecular genetic method used was NGS technology using targeted semiconductor sequencing (Ion Gene Studio S5 Plus (Termofisher Scientific, USA). The DNA and RNA library was prepared with subsequent sequencing of the amplified fragments in the Ion PGM™ system. Bioinformatics analysis of the results was performed using the Ion Reporter™ Software, the Oncomine™ Focus Assay analysis module. Study results. As a result of the study, genomic changes were detected in 95% of cases of solid tumors of various localizations. Missense mutations [BRAF; KRAS; IDH1; PIK3CA] were identified in 80% of cases. Combinations of two mutations [PIK3CA, FGFR3; PIK3CA, KRAS; EGFR, JAK3; BRAF, KRAS; ALK-PIK3R1; CDKN2-, IDH2; TP53, JAK2; ROS1, FGFR1]. In 10% of cases, an increase in the number of copies of the EGFR and KRAS genes was detected, and in 10% of cases, a fusion of the gene (RNA) MET- MET.M13M15; TMPRSS2-ERG. More than 5 mutations were detected in 5% of patients, this fact was noted in patients of the older age group and the rapid development of metastases. The identified genome changes were processed by the server through the FDA, NCCN, EMA, ESMO registries to find the most suitable therapy options existing in world practice for a specific type and localization of the established mutation. Conclusion. The mutational profile of the tumor is a necessary laboratory test in the practice of a chemotherapist for personalized prescription of targeted drugs, which has a beneficial effect on the duration and quality of life.

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