Epigenetic Changes in Tumor Suppressor Genes, P15, P16, APC-3 and E-cadherin in Body Fluid

The inactivation of tumor suppressor genes by promoter methylation plays an important role in the development of cancers; it can also be used as a marker to distinguish cancerous cells from non-cancer cells. In this study, we investigated the aberrant methylation profile of the tumor suppressor genes P15, P16, APC and E-cadherin in the cells of body fluid. A methylation-specific polymerase chain reaction was performed in 31 cases of malignant effusion and 39 cases of nonmalignant effusion. Aberrant promoter methylation of P15, P16, APC and E-cadherin genes was seen in 0%, 25.8%, 35.5% and 6.5% of malignant effusion cases, respectively, whereas the frequencies were 0%, 2.6%, 2.6% and 0%, respectively, for negative control effusion. There were statistically significant differences in the aberrant methylation of P16 (p = 0.008) and APC (p = 0.018) genes between cases of malignant effusion and controls. Methylation of one of three genes (P16, E-cadherin, APC) was found in 14 out of 31 (45.2%) cases of malignant effusion, and in two out of 39 (5.1%) cases of non-malignant effusion (p = 0.000004). Concurrent methylation was found in nine out of 31 (29%) cases of malignant effusion, but in no non-malignant effusion sample. From these results, we suggest that methylation-specific polymerase chain reaction to analyze the promoters of tumor suppressor genes can distinguish between malignant effusion and benign effusion, and may help cytologists to make more accurate diagnoses.

Key Words:  body fluid , cytologist , malignant cells , methylation-specific PCR , tumor suppressor gene

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