Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization

• Published in: Cancer causes & control Vol. 23; no. 6; pp. 865 - 873
• Main Authors: Matsuda, Yasunori, Yamashita, Satoshi, Lee, Yi-Chia, Niwa, Tohru, Yoshida, Takeichi, Gyobu, Ken, Igaki, Hiroyasu, Kushima, Ryoji, Lee, Shigeru, Wu, Ming-Shiang, Osugi, Harushi, Suehiro, Shigefumi, Ushijima, Toshikazu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.06.2012; Springer Netherlands; Springer Nature B.V
• Subjects: Age; Alcohols; Alu Elements; Antigens; Antigens, Neoplasm - genetics; Average age; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer; Cancer Research; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; CpG Islands; DNA Methylation; Endoscopy; Epidemiology; Epigenetics; Epigenomics; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Female; Genetic Predisposition to Disease; Hematology; Hospitals; Humans; Long Interspersed Nucleotide Elements - genetics; Male; Medicine; Methylation; Middle Aged; Mucous Membrane - metabolism; Mucous Membrane - pathology; Neoplasm Proteins - genetics; Nucleocytoplasmic Transport Proteins - genetics; Oncology; Original Paper; P values; Polymerase chain reaction; Promoter Regions, Genetic; Public Health; Repetitive Sequences, Nucleic Acid; Squamous cell carcinoma; Surgery; Tumors; Japan; Taiwan; Epigenetics; Repetitive element; Esophageal squamous cell carcinoma; Hypomethylation; Cancer/testis antigen
• ISSN: 0957-5243; 1573-7225
• DOI: 10.1007/s10552-012-9955-4

Background: Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs).Such hypermethylation is also present in normalappearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown. Method: We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 noncancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-CJ) were measured by bisulfite pyrosequencing and quantitative methylation-specifîc PCR, respectively. Results: Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other. Conclusion: This is the first study to show the presence of global hypomethylation in ESCCs, and even in their noncancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.