INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects. METHODS: Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter. RESULTS: It was observed that, 12 out of 39 cases (23.5%) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4%, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p = 0.028) and location (p = 0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis. CONCLUSION: The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer.
INTRODUCTION:Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects. METHODS: Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter. RESULTS: It was observed that, 12 out of 39 cases (23.5%) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4%, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p = 0.028) and location (p = 0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis. CONCLUSION: The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancerpatients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancerpatients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer.
Authors: Manzoor R Mir; Nadeem Shabir; Khursheed A Wani; Sheikh Shaff; Ishraq Hussain; Manzoor A Banday; Naveed A Chikan; S Bilal; Sheikh Aejaz Journal: Asian Pac J Cancer Prev Date: 2012
Authors: Alireza Sadjadi; Mehdi Nouraie; Mohammad Ali Mohagheghi; Alireza Mousavi-Jarrahi; Reza Malekezadeh; Donald Maxwell Parkin Journal: Asian Pac J Cancer Prev Date: 2005 Jul-Sep
Authors: Francesca Pirini; Sassan Noazin; Martha H Jahuira-Arias; Sebastian Rodriguez-Torres; Leah Friess; Christina Michailidi; Jaime Cok; Juan Combe; Gloria Vargas; William Prado; Ethan Soudry; Jimena Pérez; Tikki Yudin; Andrea Mancinelli; Helen Unger; Carmen Ili-Gangas; Priscilla Brebi-Mieville; Douglas E Berg; Masamichi Hayashi; David Sidransky; Robert H Gilman; Rafael Guerrero-Preston Journal: Oncotarget Date: 2017-06-13