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      • Alu Hypomethylation in Smoke-Exposed Epithelia and Oral Squamous Carcinoma

        Puttipanyalears, Charoenchai,Subbalekha, Keskanya,Mutirangura, Apiwat,Kitkumthorn, Nakarin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

        Background: Alu elements are one of the most common repetitive sequences that now constitute more than 10% of the human genome and potential targets for epigenetic alterations. Correspondingly, methylation of these elements can result in a genome-wide event that may have an impact in cancer. However, studies investigating the genome-wide status of Alu methylation in cancer remain limited. Objectives: Oral squamous cell carcinoma (OSCC) presents with high incidence in South-East Asia and thus the aim of this study was to evaluate the Alu methylation status in OSCCs and explore with the possibility of using this information for diagnostic screening. We evaluated Alu methylation status in a) normal oral mucosa compared to OSCC; b) peripheral blood mononuclear cells (PBMCs) of normal controls comparing to oral cancer patients; c) among oral epithelium of normal controls, smokers and oral cancer patients. Materials and Methods: Alu methylation was detected by combined bisulfite restriction analysis (COBRA) at 2 CpG sites. The amplified products were classified into three patterns; hypermethylation ($^mC^mC$), partial methylation ($^uC^mC+^mC^uC$), and hypomethylation ($^uC^uC$). Results: The results demonstrate that the $%^mC^mC$ value is suitable for differentiating normal and cancer in oral tissues (p=0.0002), but is not significantly observe in PBMCs. In addition, a stepwise decrease in this value was observed in the oral epithelium from normal, light smoker, heavy smoker, low stage and high stage OSCC (p=0.0003). Furthermore, receiver operating characteristic (ROC) curve analyses demonstrated the potential of combined $%^mC$ or $%^mC^mC$ values as markers for oral cancer detection with sensitivity and specificity of 86.7% and 56.7%, respectively. Conclusions: Alu hypomethylation is likely to be associated with multistep oral carcinogenesis, and might be developed as a screening tool for oral cancer detection.

      • Alu Methylation in Serum from Patients with Nasopharyngeal Carcinoma

        Tiwawech, Danai,Srisuttee, Ratakorn,Rattanatanyong, Prakasit,Puttipanyalears, Charoenchai,Kitkumthorn, Nakarin,Mutirangura, Apiwat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

        Background: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients. Objective: To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls. Materials and Methods: Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci). Results: A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%. Conclusions: Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.

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