Соматичні генні варіант и в клітинах нерезектабельної меланоми шкіри та виявлення фармакогеномних маркерів: вплив на стратегію ефективного лікуванн я раку

• Дата: 2025
• Автори: Gulkovskyi, R., Gerashchenko, G., Bezverkhiy, A., Melnichuk, N., Mankovska, O., Marchyshak, T., Karaman, H., Krotevych, M., Trokhymych, S., Ruban, O., Tkachuk, Z., Tukalo, M., Kashuba, V.
• Формат: Стаття
• Мова: Англійська
• Опубліковано: PH Akademperiodyka 2025
• Теми: NGS; клінічна значущість; варіанти генів; меланома; фармакогеномні маркери; ефективне лікування раку
• Онлайн доступ: https://exp-oncology.com.ua/index.php/Exp/article/view/535
• Назва журналу: Experimental Oncology

The study aimed to identify the clinically relevant gene variants in unresectable cutaneous melanoma samples from Ukrainian patients using NGS technology and to investigate some pharmacogenomic markers useful for the development of cancer treat- ment strategies. Materials and Methods. 30 samples of unresectable cutaneous melanomas of various localizations and differen- tiation grades were analyzed. The Ion Torrent NGS technology of targeted gene sequencing (Custom AmpliSeq™ Cancer hotspot and Pharmacogenomic panels) was applied to identify the genetic alterations, which were classifi d using franklin by Gennox database and custom pharmacogenomic Ion Reporter Software pipeline. Results. A total of 148 different gene alterations were identifi d in 40 genes (SNVs, MNVs, INdELs) by the Cancer hotspot Panel, revealing the mutation patterns consistent with the international data. however, notable discrepancies exist, such as a high KRAS mutation rate (29.3%), predominantly in stage III tumors, suggesting their role in tumor aggressiveness and progression. We identifi d the frequent TP53 and BRAF mutations, with BRAF V600E being the most common, and observed a higher prevalence of BRAF mutations in females. TP53 mutations were prevalent (59.3%) and varied with age and sex, though their prognostic signifi ance requires further validation. A second key novel fi ding was the detection of FLT3 mutations in 22.2% of the samples, with a signifi antly higher prevalence in stage IV disease, suggesting a potential role of FLT3 in melanoma progression and warranting further investigation as a prognostic biomarker and a potential target for the existing FLT3 inhibitors. Ultimately, our pilot analysis of pharmacogenomic markers un- derscored their potential clinical utility in choosing personalized treatment decisions. for instance, the identifi ation of a patient with the rs35599367 (G/A) risk allele for adverse drug reactions underscores the value of using pharmacogenetic data to make a correct selection between approved therapies. Conclusions. Our study presents the fi st comprehensive analysis of somatic mutations and pharmacogenomic markers in unresectable cutaneous melanoma tissue samples from Ukrainian patients. We found that while common somatic variants generally align with global trends, the mutational landscape in this cohort presents several unique features: a high KRAS mutation rate and its apparent stage-specifi prevalence, and a high FLT3 mutation rate, predominantly in stage IV tumors. further validation on a larger number of samples, as well as more exhaustive analysis employ- ing alternative methods, is necessary to substantiate these fi dings and to facilitate more effective melanoma treatment.