Methylation Profile of Several Tumor Suppressor Genes in Non-Small-Cell Lung Cancer

Multiplex methylation-sensitive PCR was employed in studying the methylation of CpG islands in the RB1 , p16/CDKN2A , p15/CDKN2B , p14/ARF , CDH1 , HIC1 , and N33 5′ regions in non-small cell lung cancer (51 tumors). Methylation was observed for the two suppressor genes involved in controlling the cell cycle through the Cdk–Rb–E2F signaling pathway, RB1 (10/51, 19%) and p16 (20/51, 39%). The highest methylation frequencies were established for CDH1 (72%) and HIC1 (82%). The CpG islands of p14 and p15 proved to be nonmethylated. At least one gene was methylated in 90% (46/51) tumors and no gene, in 10% (5/51) tumors. In addition, the genes were tested for methylation in peripheral blood lymphocytes of healthy subjects. Methylation frequency significantly differed between tumors and normal cells in the case of RB1 , p16 , CDH1 , HIC1 , and N33 . Gene methylation frequency was tested for association with histological type of the tumor and stage of tumor progression. Methylation index of a panel of tumor suppressor genes was established for groups of tumors varying in clinical and morphological parameters.