Abstract【Objective】 To investigate the expression and significance of mutant gene ATM methylation of telangiectasis ataxia in esophageal squamous cell carcinoma(ESCC). 【Methods】 The methylation status of CpG island of ATM gene in 40 cases of esophageal squamous cell carcinoma was detected by bisulfite genomic sequencing (BSP) and TA clone sequencing , while normal esophageal tissue was used as the control group; immunohistochemical (SP) method was used to detect the expression of ATM protein in esophageal squamous cell carcinoma and normal tissues.【Results】 The methylation rate of CpG island of ATM gene in 40 cases of primary esophageal squamous cell carcinoma was 85.82%, which was significantly higher than that of 40 cases of adjacent normal tissues 59.59%(P<0.05). The expression of ATM protein in primary esophageal squamous cell carcinoma was significantly lower than that in normal tissues (P<0.05).【Conclusion】 The expression of ATM protein may be related to the methylation status of its gene CpG island, and its CpG island hypermethylation may lead to partial silencing of ATM protein expression, which may be a potential prognostic related factor.
[1] Toh Y,Egashira A,Yamamoto M. Epigenetic alterations and their clinical implications in esophageal squamous cell carcinoma[J].Gen Thorac Cardiovasc Surg,2013,61(5): 262-269. [2] 郑天亮,,董岩.DNA 甲基化与食管癌的发生和发展[J].武警医学,2016,27(1):85-87. [3] 乔劲鹏,彭开桂,李多杰.ATM 基因与恶性肿瘤发生关系的研究进展[J].中华全科医学,2012,10(1):101-102. [4] 樊卫,韩笑.ATM蛋白在早期食管鳞癌中的表达及临床意义[J].国际检验医学杂志,2014,35(18):2430-2434. [5] Gilad S, Khosravi R, Shkedy D,et al.Predominance of null mutations in ataxia-telangiectasia[J].Hum Mol Genet,1996,5(4):433-439. [6] Schmutte C, Jones PA. Involvement of DNA methylation in human carcinogenesis[J].Biol Chem,1998,379(4):377-388. [7] Scott CM, Joo JE, O'Callaghan N,et al.methylation of breast cancer predisposition genes in early-onset breast cancer: australian breast cancer family registry[J].PLoS One,2016 ,11(11):e0165436. [8] McCluskey LL, Chen C, Delgadillo E,et al.Differences in p16 gene methylation and expression inbenign and malignant ovarian tumors[J].Gynecol Oncol,1999, 72(1):87-92. [9] 白坚石,何忠效.DNA甲基化作用对细胞癌变的影响[J].生理科学进展,2000,31(1):50-52. [10] Geiβler AL, Geiβler M, Kottmann D,et al.ATM mutations and E-cadherin expression define sensitivity to EGFR-targeted therapy in colorectal cancer[J].Oncotarget,2017 ,8(10):17164-17190. [11] Safar AM1, Spencer H , Su X,et al.Methylation profiling of archived non small cell lung cancer:a promising prognostic system[J].Clin Cancer Res,2005, 11(12): 4400-4405. [12] Brennan K, Garcia-Closas M, Orr N, et al.Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk [J].Cancer Res,2012,72(9):2304-2313.
2019, Vol. 36 
