@article {17096,
	title = {Promoter hypermethylation of mismatch repair genes, hMLH1 and hMSH2 in oral squamous cell carcinoma},
	journal = {Oral Dis},
	volume = {15},
	number = {3},
	year = {2009},
	note = {Czerninski, R Krichevsky, S Ashhab, Y Gazit, D Patel, V Ben-Yehuda, D eng Research Support, Non-U.S. Gov{\textquoteright}t Denmark 2009/02/12 09:00 Oral Dis. 2009 Apr;15(3):206-13. doi: 10.1111/j.1601-0825.2008.01510.x. Epub 2009 Jan 16.},
	pages = {206-13},
	type = {Journal Article},
	abstract = {OBJECTIVES: Major risk factors of oral squamous cell carcinoma (OSCC) are environmental and can lead to DNA mutagenesis. Mismatch repair (MMR) system functions to repair small DNA lesions, which can be targeted for promoter hypermethylation. We therefore wanted to test whether hypermethylation of MMR genes (hMLH1, hMSH2) could contribute to oral carcinogenesis by correlating the information to patient clinical data. METHODS: Genomic DNA was extracted from 28 OSCC and six normal oral epithelium samples. The methylation status of the two MMR genes was assessed using Methylation Specific PCR after DNA modification with sodium bisulfite. Serial sections of the same tissues were immunostained with antibodies against hMLH1 and hMSH2 protein. RESULTS: Promoter hypermethylation was observed in 14/28 OSCC cases. Remarkably, 100\% of patients with multiple oral malignancies showed hypermethylation in hMLH1 or hMSH2 compared with 31.5\% of single tumor patients. In 10 cancer cases, expression of the hMLH1 and hMSH2 genes by immunostaining showed reduced or absence of expression of one of the genes, although some did not reflect the methylation status. CONCLUSIONS: Hypermethylation of hMLH1 and hMSH2 might play a role in oral carcinogenesis and may be correlated with a tendency to develop multiple oral malignancies.},
	keywords = {80 and over Carcinoma, Adaptor Proteins, Genetic/physiology, Multiple Primary/genetics/metabolism Nuclear Proteins/*genetics/metabolism Promoter Regions, Signal Transducing/*genetics/metabolism Adult Aged Aged, Squamous Cell/*genetics/metabolism DNA Mismatch Repair/*genetics DNA Repair Enzymes/genetics/metabolism Female Humans Male Methylation Middle Aged Mouth Neoplasms/*genetics/metabolism MutL Protein Homolog 1 MutS Homolog 2 Protein/*genetics/metabolism Neo},
	issn = {1601-0825 (Electronic) 1354-523X (Linking)},
	doi = {10.1111/j.1601-0825.2008.01510.x},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/19207881},
	author = {Czerninski, R. and Krichevsky, S. and Ashhab, Y. and Gazit, D. and Patel, V. and Ben-Yehuda, D.}
}
