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Article

p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients

  • Authors:
    • Abhimanyu Kumar Jha
    • Mohsen Nikbakht
    • Veena Jain
    • Neena Capalash
    • Jagdeep Kaur
  • View Affiliations / Copyright

    Affiliations: Department of Biotechnology, Panjab University, Chandigarh 160014, India, Department of Gynaecology, Mohan Dai Oswal Cancer Treatment and Research Foundation, Ludhiana 141009, India
  • Pages: 1331-1335
    |
    Published online on: March 26, 2012
       https://doi.org/10.3892/ol.2012.655
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Abstract

The aim of this study was to determine the methylation status of the p16INK4a, p14ARF and p15INK4b genes and the subsequent effect of hypermethylation on the expression of these genes in cervical cancer patients. Methylation-specific PCR (MSP) was performed to analyse the methylation status of p16INK4a, p14ARF and p15INK4b genes and was confirmed by sequencing. Reverse transcription PCR (RT-PCR) was carried out to determine changes in the expression of the genes due to hypermethylation. Hypermethylation of the p16INK4a, p14ARF and p15INK4b gene promoters was observed in 36, 8.8 and 11.2%, respectively, of 125 cervical cancer samples from a north Indian population. Methylation of p16INK4a was significantly (P<0.001) associated with the cervical cancer cases. Significant association of p16INK4a hypermethylation with passive smoking and oral contraceptive use was also observed. Methylation of p15INK4b was also found to be significant (P<0.05). Our findings did not reveal any correlation between the promoter methylation of p16INK4a, p14ARF and p15INK4b with factors, including age and human papillomavirus infection. mRNA expression was significantly reduced in patients with a methylated promoter (P<0.001) of p16INK4a compared to patients with an unmethylated promoter. In conclusion, this is the first study demonstrating significant hypermethylation of p15INK4b and p16INK4a genes among cervical cancer patients in a north Indian population, and a significant association of p16INK4a hypermethylation with passive smoking and oral contraceptive use.
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1 

Globocan. 2008, http://wwwdep.iarc.fr/globocan/database.htm.

2 

Burd EM: Human papillomavirus and cervical cancer. Clin Microbiol Rev. 16:1–17. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Virmani AK, Muller C, Rathi A, Zoechbauer-Mueller S, Mathis M and Gazdar AF: Aberrant methylation during cervical carcinogenesis. Clinical Cancer Res. 7:584–589. 2001.PubMed/NCBI

4 

Hirama T and Koeffer HP: Role of the cyclin dependent kinase inhibitors in the development of cancer. Blood. 86:841–854. 1995.PubMed/NCBI

5 

Hannon GJ and Beach D: p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 371:257–261. 1994. View Article : Google Scholar : PubMed/NCBI

6 

Liggett WH Jr and Sidransky D: Role of the p16 tumor suppressor gene in cancer. J Clin Oncol. 16:1197–1206. 1998.PubMed/NCBI

7 

Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB and Sidransky D: 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1:686–692. 1995.

8 

Zhang SJ, Endo S, Ichikawa T, Washiyama K and Kumanishi T: Frequent deletion and 5 CpG island methylation of the p16 gene in primary malignant lymphoma of the brain. Cancer Res. 58:1231–1237. 1998.PubMed/NCBI

9 

Esteller M, Corn PG, Baylin SB and Herman JG: A gene hypermethylation profile of human cancer. Cancer Res. 61:3225–3229. 2001.PubMed/NCBI

10 

Rocco JW and Sidransky D: p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res. 264:42–55. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Feng Q, Balasubramanian A, Hawes SE, Toure P, Sow PS, Dem A, Dembele B, Critchlow CW, Xi L, Lu H, McIntosh MW, Young AM and Kiviat NB: Detection of hypermethylated genes in women with and without cervical neoplasia. J Natl Cancer Inst. 97:273–282. 2005. View Article : Google Scholar : PubMed/NCBI

12 

D’Costa J, Saranath D, Dedhia P, Sanghvi V and Mehta RA: Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India. Oral Oncol. 34:413–420. 1998.PubMed/NCBI

13 

Park JS, Dong SM, Kim HS, Lee JY, Jong Um S, Park IS, Kim SJ and Namkoong SE: Detection of p16 gene alteration in cervical cancer using tissue microdissection and LOH study. Cancer Lett. 136:101–108. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Yeh KT, Chang GA, Lin TH, Wang YF, Tien N, Chang JY, Chen CJ and Shih MC: Epigenetics changes of tumor suppressor genes, p15, p16, VHIL and p53 in oral cancer. Oncol Rep. 10:659–663. 2003.PubMed/NCBI

15 

Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB and Herman JG: Hypermethylation-associated inactivation of p14ARF is independent of p16INK4a methylation and p53 mutational status. Cancer Res. 60:129–133. 2000.

16 

Herman JG, Jen J, Merlo A and Baylin SB: Hypermethylation associated inactivation indicates a tumor suppressor role for p15INK4b. Cancer Res. 56:722–727. 1996.PubMed/NCBI

17 

Perrone F, Tabano S, Colombo F, Dagrada G, Birindelli S, Gronchi A, Colecchia M, Pierotti MA and Pilotti S: p15INK4b, p14ARF and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. Clinical Cancer Research. 9:4132–4138. 2003.

18 

Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ and Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 189:12–19. 1999. View Article : Google Scholar : PubMed/NCBI

19 

Tay SK and Tay KJ: Passive cigarette smoking is a risk factor for cervical neoplasia. Gynecol Oncol. 93:116–120. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Louie KS, de Sanjose S, Diaz M, Castellsagué X, Herrero R, Meijer CJ, Shah K, Franceschi S, Muñoz N and Bosch FX; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries. Br J Cancer. 100:1191–1197. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Jha AK, Nikbakht M, Parashar G, Shrivastava A, Capalash N and Kaur J: Reversal of hypermethylation and reactivation of the RARβ2 gene by natural compounds in cervical cancer lines. Folia Biol (Praha). 56:195–200. 2010.PubMed/NCBI

22 

Jha AK, Kumar S, Nikbakht M, Sharma V and Kaur J: Epigenetics and its role in ageing and cancer. J Med Med Sci. 2:696–713. 2011.

23 

Narayan G, Arias-Pulido H, Koul S, Vargas H, Zhang FF, Villella J, Schneider A, Terry MB, Mansukhani M and Murty VV: Frequent promoter methylation of CDH1, DAPK, RARβ and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer. 2:242003.PubMed/NCBI

24 

Ishida E, Nakamura M, Ikuta M, Shimada K, Matsuyoshi S, Kirita T and Konishi N: Promotor hypermethylation of p14ARF is a key alteration for progression of oral squamous cell carcinoma. Oral Oncol. 41:614–622. 2005.

25 

Kurakawa E, Shimamoto T and Utsumi K: Hypermethylation of p16INK4a and p15INK4b gene in non-small cell lung cancer. Int J Oncol. 19:277–281. 2001.

26 

Jeong DH, Youm MY, Kim NY, Lee KB, Sung MS, Yoon HK and Kim KT: Promoter methylation of p16, DAPK, CDH1 and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics. Int J Gynecol Cancer. 16:1234–1240. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Tripathi A, Banerjee S, Roy A, Roychowdhury S and Panda CK: Alterations of the p16 gene in uterine cervical carcinoma from Indian patients. Int J Gynecol Cancer. 13:472–479. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Attaleb M, El hamadani W, Khyatti M, Benbacer L, Benchekroun N, Benider A, Amrani M and El Mzibri M: Status of p16INK4a and E-cadherin gene promoter methylation in Moroccan patients with cervical carcinoma. Oncol Res. 184:185–192. 2009.

29 

Lea JS, Coleman R, Kurien A, Schorge JO, Miller SD, Minna JD and Muller YC: Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis. Am J Obstet Gynecol. 190:674–679. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jha AK, Nikbakht M, Jain V, Capalash N and Kaur J: p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients. Oncol Lett 3: 1331-1335, 2012.
APA
Jha, A.K., Nikbakht, M., Jain, V., Capalash, N., & Kaur, J. (2012). p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients. Oncology Letters, 3, 1331-1335. https://doi.org/10.3892/ol.2012.655
MLA
Jha, A. K., Nikbakht, M., Jain, V., Capalash, N., Kaur, J."p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients". Oncology Letters 3.6 (2012): 1331-1335.
Chicago
Jha, A. K., Nikbakht, M., Jain, V., Capalash, N., Kaur, J."p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients". Oncology Letters 3, no. 6 (2012): 1331-1335. https://doi.org/10.3892/ol.2012.655
Copy and paste a formatted citation
x
Spandidos Publications style
Jha AK, Nikbakht M, Jain V, Capalash N and Kaur J: p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients. Oncol Lett 3: 1331-1335, 2012.
APA
Jha, A.K., Nikbakht, M., Jain, V., Capalash, N., & Kaur, J. (2012). p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients. Oncology Letters, 3, 1331-1335. https://doi.org/10.3892/ol.2012.655
MLA
Jha, A. K., Nikbakht, M., Jain, V., Capalash, N., Kaur, J."p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients". Oncology Letters 3.6 (2012): 1331-1335.
Chicago
Jha, A. K., Nikbakht, M., Jain, V., Capalash, N., Kaur, J."p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients". Oncology Letters 3, no. 6 (2012): 1331-1335. https://doi.org/10.3892/ol.2012.655
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