A Breakthrough In Gastric Carcinogenesis

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Cancer / Oncology;  Genetics
Article Date: 12 Jun 2009 - 4:00 PDT

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Checkpoint with forkhead and ring finger (CHFR) is a mitotic stress checkpoint gene whose promoter is frequently methylated in various kinds of cancer. In gastric cancer, CHFR promoter hypermethylation has been reported to lead to chromosome instability (CIN) and genetic instability is one of the hallmarks of human cancer.

A research team led by Dr Eiji Oki from Kyushu University examined the methylation status of the promoter region of CHFR and microsatellite instability (MIN) status in primary gastric cancers. Their study was published on May 28, 2009 in the World Journal of Gastroenterology.

They investigated the promoter methylation of CHFR in 59 cases of gastric cancer using methylation-specific PCR. Five microsatellite loci were analyzed using high-intensity microsatellite analysis reported previously, and p53 gene mutations were investigated by direct sequencing.

They found that twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. The promoter methylation of CHFR was frequently accompanied with MIN. Seven of 20 (35.0%) cases showed MIN in hypermethylation of the CHFR tumor, while three of 39 (7.7%) cases showed MIN in the non-methylated CHFR tumor (P < 0.01). However, they failed to find any relationship between CHFR methylation and p53 mutation status.

In conclusion, they demonstrated a correlation between the hypermethylation of CHFR and the MIN of gastric cancer patients. Both MIN and CHFR hypermethylation induce mitotic check point disruption and confer a survival advantage to the cells, however, this survival advantage does not lead to either p53 mutation or CIN in gastric cancer.

This is the first study to show the striking relationship between CHFR silencing and microsatellite alteration in gastric cancer.

Reference:
Oki E, Zhao Y, Yoshida R, Masuda T, Ando K, Sugiyama M, Tokunaga E, Morita M, Kakeji Y, Maehara Y. Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer. World J Gastroenterol 2009; 15(20): 2520-2525.

Correspondence to:
Eiji Oki, MD, PhD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Source:
Lai-Fu Li
World Journal of Gastroenterology