Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer

The relationship of aberrant DNA hypermethylation of cell cycle checkpointgenes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR(checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanesin endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFRin 12.0% (6/50) of endometrial cancerspecimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p<0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanesbut became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFRalso exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFRin endometrial cancer, and our results suggest that the methylation status of CHFRmay be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.