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.
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.
Authors: Kevin D Brown; Abhilasha Rathi; Ravindra Kamath; Dillon I Beardsley; Qimin Zhan; Jennifer L Mannino; R Baskaran Journal: Nat Genet Date: 2002-11-25 Impact factor: 38.330
Authors: Petr Cejka; Lovorka Stojic; Nina Mojas; Anna Marie Russell; Karl Heinimann; Elda Cannavó; Massimiliano di Pietro; Giancarlo Marra; Josef Jiricny Journal: EMBO J Date: 2003-05-01 Impact factor: 11.598
Authors: Martin A Nowak; Natalia L Komarova; Anirvan Sengupta; Prasad V Jallepalli; Ie-Ming Shih; Bert Vogelstein; Christoph Lengauer Journal: Proc Natl Acad Sci U S A Date: 2002-11-21 Impact factor: 11.205
Authors: Jorge L Sepulveda; Jorge L Gutierrez-Pajares; Aesis Luna; Yuan Yao; John W Tobias; Steven Thomas; Yanghee Woo; Federico Giorgi; Elena V Komissarova; Andrea Califano; Timothy C Wang; Antonia R Sepulveda Journal: Mod Pathol Date: 2016-01-15 Impact factor: 7.842