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01.09.2014 | Research Article | Ausgabe 9/2014

Tumor Biology 9/2014

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

Zeitschrift:
Tumor Biology > Ausgabe 9/2014
Autoren:
Rahul Bhagat, Sandeep Sriram Kumar, Shilpa Vaderhobli, Chennagiri S. Premalata, Venkateshaiah Reddihalli Pallavi, Gawari Ramesh, Lakshmi Krishnamoorthy
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s13277-014-2136-1) contains supplementary material, which is available to authorized users.

Abstract

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-β 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-β 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-β 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-β 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-β. A significant correlation of p16 promoter methylation was observed with reduced gene expression in EOC. For RAR-β, no significant correlation was observed between promoter methylation and gene expression. Our results suggest that epigenetic alterations of p16 and RAR-β have an important role in ovarian carcinogenesis and that mechanism along with methylation plays a significant role in downregulation of RAR-β gene in ovarian cancer.

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Zusatzmaterial
Supplementary Table S1 (DOCX 13 kb)
13277_2014_2136_MOESM1_ESM.docx
Supplementary Table S2 (DOCX 11 kb)
13277_2014_2136_MOESM2_ESM.docx
Literatur
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