Epigenetic alteration of p16 and retinoic acid receptor beta genes in the development of epithelial ovarian carcinoma

被引：25
作者：
Bhagat, Rahul [1 ]
Kumar, Sandeep Sriram [1 ]
Vaderhobli, Shilpa [1 ]
Premalata, Chennagiri S. [2 ]
Pallavi, Venkateshaiah Reddihalli [3 ]
Ramesh, Gawari [1 ]
Krishnamoorthy, Lakshmi [4 ]
机构：
[1] Kidwai Mem Inst Oncol, Dept Biochem, Bangalore 560029, Karnataka, India
[2] Kidwai Mem Inst Oncol, Dept Pathol, Bangalore 560029, Karnataka, India
[3] Kidwai Mem Inst Oncol, Dept Gynaec Oncol, Bangalore 560029, Karnataka, India
[4] Sri Shankara Canc Hosp & Res Ctr, Dept Lab Med, Bangalore 560004, Karnataka, India
来源：
TUMOR BIOLOGY | 2014年 / 35卷 / 09期
关键词：
Ovarian carcinoma; p16; RAR-beta; MSP; Gene expression; TUMOR-SUPPRESSOR GENES; PROMOTER HYPERMETHYLATION; DNA METHYLATION; BREAST-CANCER; HIGH-FREQUENCY; RAR-BETA; EXPRESSION; CELL; INACTIVATION; PROGNOSIS;
D O I：
10.1007/s13277-014-2136-1
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Silencing of tumor suppressor and tumor-related genes by promoter hypermethylation is one of the major events in ovarian carcinogenesis. In this study, we analyzed aberrant promoter methylation of p16 and RAR-beta genes in 134 epithelial ovarian carcinomas (EOCs), 23 low malignant potential (LMP) tumors, 26 benign cystadenomas, and 15 normal ovarian tissues. Methylation was investigated by methylation-specific PCR (MSP), and the results were confirmed by bisulfite DNA sequencing. Relative gene expression of p16 and RAR-beta was done using quantitative reverse transcriptase PCR (qRT-PCR) on 51 EOC cases, 9 LMP tumors, and 7 benign cystadenomas with 5 normal ovarian tissues. Aberrant methylation for p16 and RAR-beta was present in 43 % (58/134) and 31 % (41/134) in carcinoma cases, 22 % (05/23) and 52 % (12/23) in LMP tumors, and 42 % (11/26) and 69 % (18/26) in benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of p16 and RAR-beta was significantly downregulated in EOC and LMP tumors than the corresponding normal tissues whereas the expression level was normal in benign cystadenomas for p16 and slightly reduced for RAR-beta. A significant correlation of p16 promoter methylation was observed with reduced gene expression in EOC. For RAR-beta, no significant correlation was observed between promoter methylation and gene expression. Our results suggest that epigenetic alterations of p16 and RAR-beta have an important role in ovarian carcinogenesis and that mechanism along with methylation plays a significant role in downregulation of RAR-beta gene in ovarian cancer.
引用
收藏
页码：9069 / 9078
页数：10
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