Methylation Analysis of Cancer-related Genes in Non-neoplastic Cells from Patients with Oral Squamous Cell Carcinoma

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2011 Mar 8

PMID 21380558

Citations 10

Authors

Melissa de Freitas Cordeiro-Silva

Zilda Fagundes Lima Oliveira

Jose Roberto Vasconcelos de Podesta

Sonia Alves Gouvea

Sandra Ventorin von Zeidler

Iuri Drumond Louro

Affiliations

Soon will be listed here.

Abstract

Early detection of Oral Squamous Cell Carcinoma (OSCC) is important to reduce mortality rates and to help provide successful cancer treatment. Hypermethylation of CpG islands is a common epigenetic mechanism that leads to gene silencing in tumors and could be a useful biomarker in OSCC. Abnormal DNA hypermethylation can occur very early in cancer development and may be induced by exposure to environmental carcinogens. We set out to investigate the methylation status of cancer-related genes in normal oral exfoliated cells from OSCC patients and healthy volunteers, as well as possible associations with alcohol/tobacco exposure or specific tumor characteristics. The methylation status of CDKN2A (cyclin-dependent kinase inhibitor 2A or p16), SFN (stratifin or 14-3-3 σ), EDNRB (endothelin receptor B) and RUNX3 (runt-related transcript factor-3) was evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in non-neoplastic oral epithelial cells from OSCC patients (n = 70) and cancer-free subjects (n = 41). Hypermethylation was observed in CDKN2A, EDNRB and SFN genes, whereas no methylation was found in the RUNX3 gene. CDKN2A hypermethylation occurred only in the OSCC group (5.7%) while SFN and EDNRB hypermethylation occurred in both groups. There was no association between hypermethylation and smoking, drinking habits or specific tumor characteristics.

Citing Articles

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References

Rosas S, Koch W, da Costa Carvalho M, Wu L, Califano J, Westra W . Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res. 2001; 61(3):939-42. View

Bender C, Pao M, Jones P . Inhibition of DNA methylation by 5-aza-2'-deoxycytidine suppresses the growth of human tumor cell lines. Cancer Res. 1998; 58(1):95-101. View

Gao F, Huang C, Lin M, Wang Z, Shen J, Zhang H . Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas. J Cancer Res Clin Oncol. 2008; 135(5):739-47. DOI: 10.1007/s00432-008-0508-x. View

Kim W, Kim E, Jeong P, Quan C, Kim J, Li Q . RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors. Cancer Res. 2005; 65(20):9347-54. DOI: 10.1158/0008-5472.CAN-05-1647. View

Zochbauer-Muller S, Lam S, Toyooka S, Virmani A, Toyooka K, Seidl S . Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int J Cancer. 2003; 107(4):612-6. DOI: 10.1002/ijc.11458. View

Scully C, Field J, Tanzawa H . Genetic aberrations in oral or head and neck squamous cell carcinoma 3: clinico-pathological applications. Oral Oncol. 2000; 36(5):404-13. DOI: 10.1016/s1368-8375(00)00023-3. View

von Zeidler S, Miracca E, Nagai M, Birman E . Hypermethylation of the p16 gene in normal oral mucosa of smokers. Int J Mol Med. 2004; 14(5):807-11. DOI: 10.3892/ijmm.14.5.807. View

Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D . Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res. 2007; 67(3):876-80. DOI: 10.1158/0008-5472.CAN-06-2995. View

Nelson J, Lee W, Nguyen S, Jarrard D, Brooks J, Magnuson S . Methylation of the 5' CpG island of the endothelin B receptor gene is common in human prostate cancer. Cancer Res. 1997; 57(1):35-7. View

10.

Morse D, Katz R, Pendrys D, Holford T, Krutchkoff D, Eisenberg E . Smoking and drinking in relation to oral epithelial dysplasia. Cancer Epidemiol Biomarkers Prev. 1996; 5(10):769-77. View

11.

Kato K, Hara A, Kuno T, Mori H, Yamashita T, Toida M . Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa. J Cancer Res Clin Oncol. 2006; 132(11):735-43. DOI: 10.1007/s00432-006-0122-8. View

12.

Bhawal U, Tsukinoki K, Sasahira T, Sato F, Mori Y, Muto N . Methylation and intratumoural heterogeneity of 14-3-3 sigma in oral cancer. Oncol Rep. 2007; 18(4):817-24. View

13.

FERGUSON A, Evron E, Umbricht C, Pandita T, Chan T, Hermeking H . High frequency of hypermethylation at the 14-3-3 sigma locus leads to gene silencing in breast cancer. Proc Natl Acad Sci U S A. 2000; 97(11):6049-54. PMC: 18556. DOI: 10.1073/pnas.100566997. View

14.

Christensen B, Houseman E, Marsit C, Zheng S, Wrensch M, Wiemels J . Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009; 5(8):e1000602. PMC: 2718614. DOI: 10.1371/journal.pgen.1000602. View

15.

Spitz M . Epidemiology and risk factors for head and neck cancer. Semin Oncol. 1994; 21(3):281-8. View

16.

Parkin D, Laara E, Muir C . Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer. 1988; 41(2):184-97. DOI: 10.1002/ijc.2910410205. View

17.

Li Q, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi X . Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 2002; 109(1):113-24. DOI: 10.1016/s0092-8674(02)00690-6. View

18.

Jones P, Laird P . Cancer epigenetics comes of age. Nat Genet. 1999; 21(2):163-7. DOI: 10.1038/5947. View

19.

Pattani K, Zhang Z, Demokan S, Glazer C, Loyo M, Goodman S . Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy. Cancer Prev Res (Phila). 2010; 3(9):1093-103. PMC: 2945229. DOI: 10.1158/1940-6207.CAPR-10-0115. View

20.

Christensen B, Houseman E, Godleski J, Marsit C, Longacker J, Roelofs C . Epigenetic profiles distinguish pleural mesothelioma from normal pleura and predict lung asbestos burden and clinical outcome. Cancer Res. 2009; 69(1):227-34. PMC: 2744125. DOI: 10.1158/0008-5472.CAN-08-2586. View