Promoter methylation of p16, Runx3, DAPK and CHFR genes is frequent in gastric carcinoma

被引：33
作者：
Hu, Shi-Lian [1 ]
Kong, Xiang-Yong [1 ]
Cheng, Zhao-Dong [1 ]
Sun, Yu-Bei [2 ]
Shen, Gan [3 ]
Xu, Wei-Ping [4 ]
Wu, Lei [4 ]
Xu, Xiu-Cai [5 ]
Jiang, Xiao-Dong [1 ]
Huang, Da-Bing [1 ]
机构：
[1] Anhui Med Univ, Dept Geriatr, Affiliated Anhui Prov Hosp, Hefei 230001, Peoples R China
[2] Anhui Prov Hosp, Dept Oncol, Hefei, Peoples R China
[3] Cadres Ward Anhui PPC Hosp, Hefei, Peoples R China
[4] Anhui Evidence Based Med Ctr, Hefei, Peoples R China
[5] Anhui Prov Hosp Ctr Lab, Hefei, Peoples R China
来源：
TUMORI JOURNAL | 2010年 / 96卷 / 05期
基金：
中国国家自然科学基金;
关键词：
gastric carcinoma; p16; Runx3; DAPK; CHFR; DNA methylation; CPG-ISLAND METHYLATION; ABERRANT METHYLATION; MICROSATELLITE INSTABILITY; DNA METHYLATION; COMPREHENSIVE ANALYSIS; HUMAN CANCERS; CELL-CYCLE; HYPERMETHYLATION; EXPRESSION; KINASE;
D O I：
10.1177/030089161009600515
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Aims and background. Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including gastric cancer. A number of reports on methylation of various genes in gastric cancer have been published, but most of these studies focused on cancer tissues or only a single gene. In this study, we determined the promoter hypermethylation status and mRNA expression of 4 genes: p16, Runx3, DAPK and CHFR. Methods. Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of p16, Runx3, DAPK and CHFR gene promoters in cancer and adjacent normal gastric mucosa specimens from 70 patients with gastric cancer, as well as normal gastric biopsy samples from 30 people without cancer serving as controls. In addition, the mRNA expression of p16, Runx3, DAPK and CHFR was investigated in 34 gastric cancer patients by RT-PCR. Bisulfite DNA sequence analysis was applied to check the positive samples detected by MSP. Results. When carcinoma specimens were compared with adjacent normal gastric mucosa samples, a significant increase in promoter methylation of p16, Runx3, DAPK and CHFR was observed, while all 30 histologically normal gastric specimens were methylation free for all 4 genes. The methylation rate of the 4 genes increased from normal stomach tissue to tumor-adjacent gastric mucosa to gastric cancer tissue. Concurrent methylation in 2 or more genes was found in 22.9% of tumor-adjacent normal gastric mucosa and 75.7% of cancer tissues. No correlation was found between hypermethylation and other clinicopathological parameters such as sex, age, and tumor location. However, the frequency of DAPK and CHFR methylation in cancer tissues was significantly associated with the extent of differentiation and lymph node metastasis (P <0.05) and the frequency of Runx3 methylation was significantly associated with tumor size (P <0.05). Weak expression and loss of expression of the 4 genes was observed in cancer tissues and was significantly associated with promoter hypermethylation (P <0.05). Conclusions. Promoter hypermethylation of p16, Runx3, DAPK and CHFR is frequent in gastric cancer. DAPK and CHFR promoter hypermethylation may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. Weak gene expression and loss of gene expression due to promoter hypermethylation may be a cancer-specific event. Free full text available at www.tumorionline.it
引用
收藏
页码：726 / 733
页数：8
相关论文
共 52 条
[1]   CLONING, MAPPING AND EXPRESSION OF PEBP2-ALPHA-C, A 3RD GENE ENCODING THE MAMMALIAN RUNT DOMAIN [J].
BAE, SC ;
TAKAHASHI, E ;
ZHANG, YW ;
OGAWA, E ;
SHIGESADA, K ;
NAMBA, Y ;
SATAKE, M ;
ITO, Y .
GENE, 1995, 159 (02) :245-248
[2]   RATES OF P16(MTS1) MUTATIONS IN PRIMARY TUMORS WITH 9P LOSS [J].
CAIRNS, P ;
MAO, L ;
MERLO, A ;
LEE, DJ ;
SCHWAB, D ;
EBY, Y ;
TOKINO, K ;
VANDERRIET, P ;
BLAUGRUND, JE ;
SIDRANSKY, D .
SCIENCE, 1994, 265 (5170) :415-416
[3]   CpG island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus [J].
Chang, Moon-Sung ;
Uozaki, Hiroshi ;
Chong, Ja-Mun ;
Ushiku, Tetsuo ;
Sakuma, Kazuya ;
Ishikawa, Shunpei ;
Hino, Rumi ;
Barua, Rita Rani ;
Iwasaki, Yoshiaki ;
Arai, Kuniyoshi ;
Fujii, Hideki ;
Nagai, Hideo ;
Fukayama, Masashi .
CLINICAL CANCER RESEARCH, 2006, 12 (10) :2995-3002
[4]   Cell cycle - Conducting the mitotic symphony [J].
Cortez, D ;
Elledge, SJ .
NATURE, 2000, 406 (6794) :354-356
[5]   Aberrant CpG-island methylation has non-random and tumour-type-specific patterns [J].
Costello, JF ;
Frühwald, MC ;
Smiraglia, DJ ;
Rush, LJ ;
Robertson, GP ;
Gao, X ;
Wright, FA ;
Feramisco, JD ;
Peltomäki, P ;
Lang, JC ;
Schuller, DE ;
Yu, L ;
Bloomfield, CD ;
Caligiuri, MA ;
Yates, A ;
Nishikawa, R ;
Huang, HJS ;
Petrelli, NJ ;
Zhang, XL ;
O'Dorisio, MS ;
Held, WA ;
Cavenee, WK ;
Plass, C .
NATURE GENETICS, 2000, 24 (02) :132-138
[6]  
Du Y, 2001, CANCER RES, V61, P8094
[7]   CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future [J].
Esteller, M .
ONCOGENE, 2002, 21 (35) :5427-5440
[8]   Timeline - The history of cancer epigenetics [J].
Feinberg, AP ;
Tycko, B .
NATURE REVIEWS CANCER, 2004, 4 (02) :143-153
[9]  
Gao Nan, 2008, Zhonghua Zhongliu Zazhi, V30, P361
[10]   Mechanism and pathobiologic implications of CHFR promoter methylation in gastric carcinoma [J].
Gao, Yu-Jia ;
Xin, Yan ;
Zhang, Jian-Jun ;
Zhou, Jin .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (32) :5000-5007
123456