Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer

Eiji Oki, Yan Zhao, Rintaro Yoshida, Takanobu Masuda, Kouji Andou, Masahiiko Sugiyama, Eriko Tokunaga, Masaru Morita, Yoshihiro Kakeji, Yoshihiko Maehara

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Abstract

Aim: To examine the methylation status of the promoter region of the checkpoint with forkhead-associated and ring finger (CHFR) and microsatellite mutator status in 59 primary gastric cancers. Methods: We 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. Results: Twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. We found that the promoter methylation of CHFR was frequently accompanied with microsatellite instability (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, we failed to find any relationship between CHFR methylation and p53 mutation status. Conclusion: The coordinated loss of both the mitotic check point function and mismatch repair system suggests the potential to overcome the cell cycle check point, which may lead to an accumulation of mutations. However, the p53 mutation was not related to hypermethylation of the CHFR promoter and MIN, which indicates that an abnormality in p53 occurs as an independent process from the mismatch repair deficiency in carcinogenesis.

Original languageEnglish
Pages (from-to)2520-2525
Number of pages6
JournalWorld Journal of Gastroenterology
Volume15
Issue number20
DOIs
Publication statusPublished - May 28 2009

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Microsatellite Instability
Methylation
Fingers
Stomach Neoplasms
Microsatellite Repeats
Mutation
DNA Mismatch Repair
p53 Genes
Genetic Promoter Regions
Neoplasms
Cell Cycle
Carcinogenesis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer. / Oki, Eiji; Zhao, Yan; Yoshida, Rintaro; Masuda, Takanobu; Andou, Kouji; Sugiyama, Masahiiko; Tokunaga, Eriko; Morita, Masaru; Kakeji, Yoshihiro; Maehara, Yoshihiko.

In: World Journal of Gastroenterology, Vol. 15, No. 20, 28.05.2009, p. 2520-2525.

Research output: Contribution to journalArticle

Oki, Eiji ; Zhao, Yan ; Yoshida, Rintaro ; Masuda, Takanobu ; Andou, Kouji ; Sugiyama, Masahiiko ; Tokunaga, Eriko ; Morita, Masaru ; Kakeji, Yoshihiro ; Maehara, Yoshihiko. / Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer. In: World Journal of Gastroenterology. 2009 ; Vol. 15, No. 20. pp. 2520-2525.
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T1 - Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer

AU - Oki, Eiji

AU - Zhao, Yan

AU - Yoshida, Rintaro

AU - Masuda, Takanobu

AU - Andou, Kouji

AU - Sugiyama, Masahiiko

AU - Tokunaga, Eriko

AU - Morita, Masaru

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

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N2 - Aim: To examine the methylation status of the promoter region of the checkpoint with forkhead-associated and ring finger (CHFR) and microsatellite mutator status in 59 primary gastric cancers. Methods: We 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. Results: Twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. We found that the promoter methylation of CHFR was frequently accompanied with microsatellite instability (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, we failed to find any relationship between CHFR methylation and p53 mutation status. Conclusion: The coordinated loss of both the mitotic check point function and mismatch repair system suggests the potential to overcome the cell cycle check point, which may lead to an accumulation of mutations. However, the p53 mutation was not related to hypermethylation of the CHFR promoter and MIN, which indicates that an abnormality in p53 occurs as an independent process from the mismatch repair deficiency in carcinogenesis.

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