THE TRANSCRIPTOME ANALYSIS OF A MODEL OF THYROID CANCER WITH NRAS(Q61R) MUTATION. Homo sapiens

Q61R mutation of NRAS gene is one of the most frequent driver mutations of thyroid cancer. The tumors with this mutation are characterized by invasion into blood vessels and formation of distant metastases. To study the role of this mutation in the growth of thyroid cancer we developed a model system on the basis of thyroid epithelial cell line Nthy-ori 3-1 transduced by lentiviral vector containing NRAS gene with Q61R mutation. To estimate the impact of this mutation on the development of oncogenic processes we performed comparative transcriptome analysis of this derivative of Nthy-ori 3-1 cell line and the derivatives obtained by transduction of these cells with “empty” viral vector and the vector containing wild type NRAS gene. The obtained data were compared to the data of transcriptome analysis of thyroid tumors containing Q61R mutation of NRAS gene and the tumors with other driver mutations. The expression of NRAS gene with Q61R mutation causes the expression changes in the model cell line that are characteristic of the tumors with the same driver mutation. It was shown on the model cell line that the expression of NRAS with Q61R mutation leads to the expression change of genes responsible for the epithelial-mesenchymal transition and cellular invasion. The alteration in the expression of these genes affects the phenotype of the model cells that acquire the traits of mesenchymal cells and demonstrate increased ability to invasive growth.