Aberrant promoter hypermethylation of RAR-β in endometrial carcinoma- an Indian study.

  • Nagaratna Shivanandappa Research Scholar, Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
  • Dr. Shalini N Swamy Research Scholar, Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
  • Dr. Sandeep Kumar S Senior Research Fellow, Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
  • Dr. Suma Sheshadri Associate Professor Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
  • Dr. Venkateshaiah Reddihalli Pallavi Professor, Department of Gynaecology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
  • Dr. Ramesh Gawari Professor, Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
DOI: https://doi.org/10.17511/ijmrr.2021.i03.05
Keywords: DNA Hypermethylation, RAR-β, endometrial cancer, epigenetic alterations, DNA hypermethylation, Methylation specific PCR.

Abstract

Endometrial cancer is the seventh most common cancer in women worldwide with and age standardized rate of 8.4 per 100,000 women. Epigenetic alterations such as promoter hypermethylation of TSGs are known to be early events in carcinogenesis. The aim of the present study, we assessed the aberrant promoter hypermethylation pattern of RAR-β in 78 endometrial cancer samples.

Methods: DNA was isolated from endometrial carcinoma samples and normal tissues and aberrant promoter hypermethylation was assessed using nested and methylation specific PCR. Chi square test was used for statistical analysis and a p-value<0.05 was considered to be statistically significant.

Results: 40 of the 78 (51.28%) endometrial carcinoma sample showed aberrant hypermethylation of RAR-β gene. Methylation status in each histological subtype, grade and stage of the disease was also assessed.

Conclusion: Aberrant hypermethylation is an important early epigenetic alteration that occurs during tumorigenesis. The Data shown here reports that promoter hypermethylation of RAR-β occurs in endometrial carcinoma and therefore could be used as a potential marker for early diagnosis and prognosis of the disease.

Downloads

Download data is not yet available.

References

Banno K, Kisu I, Yanokura M, Masuda K, Kobayashi Y, Ueki A, et al. Endometrial Cancer and Hypermethylation: Regulation of DNA and MicroRNA by Epigenetics. Biochem Res Int. 2012;2012:738274. doi: 10.1155/2012/738274.

World Health Organization. "Global cancer observatory." Cancer today. Available from: https://gco.iarc.fr//(accessed on 23 Oct, 2020) (2019).

Balasubramaniam G, Sushama S, Rasika B, Mahantshetty U. Hospital-based study of endometrial cancer survival in Mumbai, India. Asian Pac J Cancer Prev. 2013;14(2):977-80. doi: 10.7314/apjcp.2013.14.2.977.

Fan Y, Wang Y, Fu S, Yang L, Lin S, Fan Q, et al. The diagnostic role of DNA methylation in sporadic endometrial cancer: a systematic review and meta-analysis. Oncotarget. 2017 Dec 20;9(9):8642-8652. doi: 10.18632/oncotarget.23480.

S SK, Swamy SN, Premalatha CS, Pallavi VR, Gawari R. Aberrant Promoter Hypermethylation of RASSF1a and BRCA1 in Circulating Cell-Free Tumor DNA Serves as a Biomarker of Ovarian Carcinoma. Asian Pac J Cancer Prev. 2019 Oct 1;20(10):3001-3005. doi: 10.31557/APJCP.2019.20.10.3001.

Sun SY, Lotan R. Retinoids and their receptors in cancer development and chemoprevention. Crit Rev Oncol Hematol. 2002 Jan;41(1):41-55. doi: 10.1016/s1040-8428(01)00144-5.

Altucci L, Gronemeyer H. Decryption of the retinoid death code in leukemia. J Clin Immunol. 2002 May;22(3):117-23. doi: 10.1023/a:1015490627613.

Xu XC, Lotan R. Aberrant expression and function of retinoid receptors in cancer. InRetinoids 1999 (pp. 323-343). Springer, Berlin, Heidelberg.

Piedrafita FJ. The biochemical and molecular basis of vitamin A and retinoid action. Retinoids. 1999:153-84.

Zou CP, Clifford JL, Xu XC, Sacks PG, Chambon P, Hong WK, Lotan R. Modulation by retinoic acid (RA) of squamous cell differentiation, cellular RA-binding proteins, and nuclear RA receptors in human head and neck squamous cell carcinoma cell lines. Cancer Res. 1994 Oct 15;54(20):5479-87.

Jones PL, Wolffe AP. Relationships between chromatin organization and DNA methylation in determining gene expression. Semin Cancer Biol. 1999 Oct;9(5):339-47. doi: 10.1006/scbi.1999.0134.

Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet. 2001 Apr;10(7):687-92. doi: 10.1093/hmg/10.7.687.

Ahuja N, Issa JP. Aging, methylation and cancer. Histol Histopathol. 2000 Jul;15(3):835-42. doi: 10.14670/HH-15.835.

Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 2000 Apr;16(4):168-74. doi: 10.1016/s0168-9525(99)01971-x.

Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002 Jun;3(6):415-28. doi: 10.1038/nrg816.

Costello JF, Frühwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000 Feb;24(2):132-8. doi: 10.1038/72785.

Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. BMC Cancer. 2006 Aug 23;6:212. doi: 10.1186/1471-2407-6-212.

Tao MH, Freudenheim JL. DNA methylation in endometrial cancer. Epigenetics. 2010 Aug 16;5(6):491-8. doi: 10.4161/epi.5.6.12431.

Jones LC, Tefferi A, Idos GE, Kumagai T, Hofmann WK, Koeffler HP. RARbeta2 is a candidate tumor suppressor gene in myelofibrosis with myeloid metaplasia. Oncogene. 2004 Oct 14;23(47):7846-53. doi: 10.1038/sj.onc.1207510.

Jones LC, Tefferi A, Idos GE, Kumagai T, Hofmann WK, Koeffler HP. RARbeta2 is a candidate tumor suppressor gene in myelofibrosis with myeloid metaplasia. Oncogene. 2004 Oct 14;23(47):7846-53. doi: 10.1038/sj.onc.1207510.

Xu XC. Tumor-suppressive activity of retinoic acid receptor-beta in cancer. Cancer Lett. 2007 Aug 8;253(1):14-24. doi: 10.1016/j.canlet.2006.11.019.

Zöchbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 2001 Jan 1;61(1):249-55.

Kim JS, Lee H, Kim H, Shim YM, Han J, Park J, et al. Promoter methylation of retinoic acid receptor beta 2 and the development of second primary lung cancers in non-small-cell lung cancer. J Clin Oncol. 2004 Sep 1;22(17):3443-50. doi: 10.1200/JCO.2004.11.135.

Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999 Jan 1;59(1):67-70. Erratum in: Cancer Res 1999 Aug 1;59(15):3853.

Virmani AK, Rathi A, Zöchbauer-Müller S, Sacchi N, Fukuyama Y, Bryant D, et al. Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. J Natl Cancer Inst. 2000 Aug 16;92(16):1303-7. doi: 10.1093/jnci/92.16.1303.

Ramesh, G., Kumar, S. S., Swamy, S. N., Premalata, C. S., & Pallavi, V. R. A Study On The Aberrant Promoter Hypermethylation Of Rar-Β Gene In The Plasma Of Epithelial Ovarian Carcinoma Patients.

Shukla S, Mirza S, Sharma G, Parshad R, Gupta SD, Ralhan R. Detection of RASSF1A and RARbeta hypermethylation in serum DNA from breast cancer patients. Epigenetics. 2006 Apr-Jun;1(2):88-93. doi: 10.4161/epi.1.2.2679.

Ivanova T, Petrenko A, Gritsko T, Vinokourova S, Eshilev E, Kobzeva V, et al. Methylation and silencing of the retinoic acid receptor-beta 2 gene in cervical cancer. BMC Cancer. 2002 Mar 21;2:4. doi: 10.1186/1471-2407-2-4.

Bhagat R, Kumar SS, Vaderhobli S, Premalata CS, Pallavi VR, Ramesh G, et al. Epigenetic alteration of p16 and retinoic acid receptor beta genes in the development of epithelial ovarian carcinoma. Tumour Biol. 2014 Sep;35(9):9069-78. doi: 10.1007/s13277-014-2136-1.

Arafa M, Kridelka F, Mathias V, Vanbellinghen JF, Renard I, Foidart JM, et al. High frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarcinoma. Histopathology. 2008 Nov;53(5):525-32. doi: 10.1111/j.1365-2559.2008.03147.x.

Li R, Saito T, Tanaka R, Satohisa S, Adachi K, Horie M, et al. Hypermethylation in promoter region of retinoic acid receptor-beta gene and immunohistochemical findings on retinoic acid receptors in carcinogenesis of endometrium. Cancer Lett. 2005 Feb 28;219(1):33-40. doi: 10.1016/j.canlet.2004.06.044.

Banno K, Yanokura M, Susumu N, Kawaguchi M, Hirao N, Hirasawa A, et al. Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer. Oncol Rep. 2006 Dec;16(6):1189-96.

Seeber LM, Zweemer RP, Marchionni L, Massuger LF, Smit VT, van Baal WM, et al. Methylation profiles of endometrioid and serous endometrial cancers. Endocr Relat Cancer. 2010 Jun 25;17(3):663-73. doi: 10.1677/ERC-10-0014.

CITATION
DOI: 10.17511/ijmrr.2021.i03.05
Published: 2021-06-30
How to Cite
1.
Nagaratna Shivanandappa, Dr. Shalini N Swamy, Dr. Sandeep Kumar S, Dr. Suma Sheshadri, Dr. Venkateshaiah Reddihalli Pallavi, Dr. Ramesh Gawari. Aberrant promoter hypermethylation of RAR-β in endometrial carcinoma- an Indian study. Int J Med Res Rev [Internet]. 2021Jun.30 [cited 2024Apr.19];9(3):160-6. Available from: https://ijmrr.medresearch.in/index.php/ijmrr/article/view/1294
Issue
Vol 9 No 3 (2021): May-Jun
Section
Original Article

Copyright (c) 2021 Author (s). Published by Siddharth Health Research and Social Welfare Society

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Most read articles by the same author(s)