A breakthrough in gastric carcinogenesis

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 will be 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.

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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. http://www.wjgnet.com/1007-9327/15/2520.asp

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. [email protected]

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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The WJG Press mainly publishes World Journal of Gastroenterology.