Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer
2007
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.
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