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Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development

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Abstract

Purpose

Tumor suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer development. The aim of this study was to assess the extent of methylation of the RASSF1A and APC TSG promoters in ovarian epithelial adenomas, low malignant potential tumours and carcinomas in order to reveal a role for epigenetic TSG silencing in the development of these ovarian malignancies.

Method

The promoter methylation status of the RASSF1A and APC genes was assessed in 19 benign cystadenomas, 14 low malignant potential (LMP) tumours, and 86 carcinomas using methylation specific PCR (MSP).

Results

The methylation frequencies of the RASSF1A and APC gene promoters in benign cystadenomas were found to be 37 % and 16 %, respectively. The LMP tumours exhibited RASSF1A and APC gene promoter methylation frequencies of 50 % and 28 %, respectively, whereas the carcinomas exhibited methylation frequencies of 58 % and 29 %, respectively. Methylation of either the RASSF1A or the APC gene promoter was encountered in 58 % of the invasive carcinomas.

Conclusion

The observed aberrant methylation frequencies of the RASSF1A and APC gene promoters indicate that an accumulation of epigenetic events at these specific TSG promoters may be associated with the malignant transformation of benign cystadenomas and LMP tumours to carcinomas.

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Acknowledgements

Rahul Bhagat acknowledges the Director General, Indian Council of Medical Research, New Delhi for providing a senior research fellowship for the present study.

Ethical clearance

The study was approved by the Institutional Ethics Committee and all samples were collected after obtaining written informed consent from the patients.

Disclosure/statement of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India

    Rahul Bhagat, Shilpa Chadaga, G. Ramesh & Lakshmi Krishnamoorthy

  2. Department of Pathology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India

    C. S. Premalata

  3. Department of Epidemiology and Biostatistics, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India

    C. Ramesh

  4. Department of Gynec Oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bangalore, 560029, India

    V. R. Pallavi

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  1. Rahul Bhagat
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Correspondence to Lakshmi Krishnamoorthy.

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Bhagat, R., Chadaga, S., Premalata, C.S. et al. Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development. Cell Oncol. 35, 473–479 (2012). https://doi.org/10.1007/s13402-012-0106-4

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  • DOI: https://doi.org/10.1007/s13402-012-0106-4

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