TRANSCRIPTOMIC ANALYSIS OF MELANOMA CELLS EXTRACTED FROM DIFFERENT SITES OF THE PRIMARY TUMOR

Introduction. Intratumor heterogeneity is a characteristic feature for most malignant tumors, including cutaneous melanoma. This property represents one of the main obstacles  for effective targeted therapy, due to the different sensitivity to chemotherapeutic agents on  various tumor cells subclones. Treatment of malignant tumors requires an individual approach to choose the most appropriate treatment regimen. The purpose of the study was to evaluate differences in melanoma tissue samples obtained from different parts of one patient’s primary tumor at the transcriptomic level. Material and Methods . Melanoma cell cultures obtained from both central and peripheral parts of the primary tumor of two patients were used in the study. Results . Subclones from different parts of the first patient’s tumor were similar, whereas the second patient demonstrated significant differences at the transcriptomic level (in 2953  transcripts out of 48226). In the cells of the central zone of the second patient’s tumor, an  increase in mRNA of the genes encoding proteins associated with tumor-specific immune  response, as well as ABC-family transport proteins and cytokine signaling molecules, were  noted. In the cells from the peripheral area of the same tumor, a more intensive transcription of genes encoding extracellular matrix and inflammatory response  proteins was observed. Taken all round, the differences between the subclones of the second  patient’s cells were relevant to some signaling cascades playing a leading role in  oncogenesis (MAPK, PI3K-Akt-mTOR, VEGFA-VEGFR2, etc.). Conclusion.  The study allowed  evaluation of differences between cancer cells within a tumor at the transcriptional level in order to search for further approaches to personalized melanoma therapy.