Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma

被引：42
作者：
Banzai, Chiaki [1 ]
Nishino, Koji [1 ]
Quan, Jinhua [1 ]
Yoshihara, Kosuke [1 ]
Sekine, Masayuki [1 ]
Yahata, Tetsuro [1 ]
Tanaka, Kenichi [1 ]
机构：
[1] Niigata Univ, Grad Sch Med & Dent Sci, Div Obstet & Gynecol, Chuo Ward, Niigata 9518510, Japan
来源：
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY | 2014年 / 19卷 / 01期
关键词：
Cervical cancer; Methylation; DAPK1; HUMAN-PAPILLOMAVIRUS; DNA METHYLATION; CANCER; HYPERMETHYLATION; PREVALENCE; P16(INK4A); SERUM; CDH1; P16;
D O I：
10.1007/s10147-013-0530-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background and objectives Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer. Methods The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels. Results The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (P < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues. Conclusion Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis.
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页码：127 / 132
页数：6
相关论文
共 30 条
[21]  
Virmani AK, 2001, CLIN CANCER RES, V7, P584
[22]   Cervical cancer [J].
Waggoner, SE .
LANCET, 2003, 361 (9376) :2217-2225
[23]  
Walboomers JMM, 1999, J PATHOL, V189, P12, DOI 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO
[24]  
2-F
[25]   CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients [J].
Widschwendter, A ;
Ivarsson, L ;
Blassnig, A ;
Müller, HM ;
Fiegl, H ;
Wiedemarz, A ;
Müller-Holzner, E ;
Goebel, G ;
Marth, C ;
Widschwendter, M .
INTERNATIONAL JOURNAL OF CANCER, 2004, 109 (02) :163-166
[26]   Analysis of aberrant DNA methylation and human papillomavirus DNA in cervicovaginal specimens to detect invasive cervical cancer and its precursors [J].
Widschwendter, A ;
Gattringer, C ;
Ivarsson, L ;
Fiegl, H ;
Schneitter, A ;
Ramoni, A ;
Müller, HM ;
Wiedemair, A ;
Jerabek, S ;
Müller-Holzner, E ;
Goebel, G ;
Marth, C ;
Widschwendter, M .
CLINICAL CANCER RESEARCH, 2004, 10 (10) :3396-3400
[27]   DNA methylation in serum and tumors of cervical cancer patients [J].
Widschwendter, A ;
Müller, HM ;
Fiegl, H ;
Ivarsson, L ;
Wiedemair, A ;
Müller-Holzner, E ;
Goebel, G ;
Marth, C ;
Widschwendter, M .
CLINICAL CANCER RESEARCH, 2004, 10 (02) :565-571
[28]   Methylation of p16INK4A in primary gynecologic malignancy [J].
Wong, YF ;
Chung, TKH ;
Cheung, TH ;
Nobori, T ;
Yu, AL ;
Yu, J ;
Batova, A ;
Lai, KWH ;
Chang, AMZ .
CANCER LETTERS, 1999, 136 (02) :231-235
[29]   Detection of hypermethylated genes in tumor and plasma of cervical cancer patients [J].
Yang, HJ ;
Liu, VWS ;
Wang, Y ;
Chan, KYK ;
Tsang, PCK ;
Khoo, US ;
Cheung, ANY ;
Ngan, HYS .
GYNECOLOGIC ONCOLOGY, 2004, 93 (02) :435-440
[30]  
Zysman M, 2002, CANCER RES, V62, P3663
123