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Preliminary Investigation Of Polymorphisms And Expression Of O~6-Methylguanine-DNA Methyltransferase Gene And Its Correlation With P53 In Chaoshan Esophageal Carcinoma

Posted on:2007-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:S H LiuFull Text:PDF
GTID:2144360185986512Subject:Pathology and pathophysiology
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Background and ObjectiveO~6- Methylguanine-DNA methyltransferase (MGMT) plays an important role in the repair of alkylating agent-induced DNA damage. The methyltransferase gene spans at least 170 kilobases and is located on human chromosome 10. MGMT can specifically repair O~6-alkylguanine adducts in DNA by transferring the adducts from DNA to a cysteine145 residue of its active site. MGMT can be detected in nucleolus or cytoplasm in most tumor cells (Mer+). O~6- Methylguanine-DNA methyltransferase (MGMT) is one of important DNA repair enzyme in repairing major premutagenetic lesions in DNA produced by alkylating agents. O~6-Alkylguanine is a one of important former mutations induced by alkylating agents. If the mutation is not repaired in time, the O~6-alkylguanine preferentially pairs with thymine rather than with cytosine during DNA replication, resulting in a GC to AT transition.The process may be correlated with p53. Different expression of MGMT in normal tissue and tumor tissue has been observed.It was reported that different activity for MGMT may have relation with the expression of p53 in tumor tissue.The relation of p53 and MGMT in Chinese Chaoshan esophageal cancer tissue hasn't been repoted yet. We performed a microarray-based method for genotype analysis to detect the polymorphisms of the MGMT codon 84 (C2740214T), codon 143 (A2798995G) and codon 160 (G2799046A) and to assess the prevalence of these polymorphisms in Chinese Chaoshan esophageal cancer patients and the healthy controls. Expression of MGMT and mtp53 was also .detected immunohistochemically in esophageal cancer tissue to found out the relation...
Keywords/Search Tags:esophageal carcinogenesis, O~6- Methylguanine-DNA methyltransferase, p53, microarray-based method
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