Potential of comprehensive somatic profiling tumor tissue for a personalized approach to treatment selection in various malignant neoplasms

Purpose of the study. Evaluation of the therapy optimization for patients with solid tumors using comprehensive genomic profiling (CGP).

Patients and methods. The article presents the results of a study involving patients from the Yamalo-Nenets Autonomous Okrug with malignant neoplasms of various localizations: breast cancer (n = 4), colorectal cancer (n = 3), gastric cancer (n = 1), cervical cancer (n = 1), ovarian cancer (n = 1), and prostate cancer (n = 1). Molecular genetic testing was performed using the Sentis™ Cancer+Discovery Panel (BGI). Biological material included FFPE tumor tissue sections containing >20 % tumor cells. Next-generation sequencing (NGS) parameters were as follows: sequencing depth > 900× for tumor samples and >300× for matched control samples (venous blood); insertion size ~140–210 bp; Q30 > 80 %; target coverage > 90 %. The analysis included 689 genes, microsatellite instability (MSI), tumor mutational burden (TMB), and germline pathogenic variants.

Results. Clinically significant somatic biomarkers were identified in 8 of 11 cases (72.7 %), enabling optimization of treatment strategies toward the most effective therapeutic approaches. In 5 of these 8 cases (62.5 %), treatment plan modification included the potential use of off-label therapy following approval by a multidisciplinary tumor board. Germline (inherited) variants were detected in 4 of 11 cases (36.4 %), indicating the need for genetic counseling and evaluation of relatives.

Conclusion. The implementation of CGP in clinical practice expands the possibilities for a personalized approach to the treatment of patients with metastatic and progressive malignant neoplasms through the identification of additional potential biomarkers of sensitivity or resistance to targeted anticancer agents and immunotherapy. Further evaluation of CGP effectiveness in a larger patient cohort appears warranted.

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