Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group

Mutlu, M; Mutlu, P; Azarkan, S; Bayır, Ö; Öcal, B; Saylam, G; Korkmaz, MH

doi:10.2478/bjmg-2020-0025

Abstract

Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey, and 48 unrelated healthy volunteers from different geographic regions of Turkey, were included in this study. Methylation status of the promoter region of the EGFR gene was detected by methylation-specific-polymerase chain reaction (MS-PCR). The correlation between EGFR gene promoter methylation profiles and clinical characteristics were examined using the χ² test. Methylation was observed in 79.0% of HNSCC patients, whereas this ratio was 90.0% in healthy individuals. The results show that promoter region methylation of the EGFR gene was not associated with HNSCC development in the studied Turkish patient group. In addition, the methylation status of the EGFR gene promoter was not found to be related to age, gender or tumor stage.

References

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics. CA Cancer J Clin. 2005; 55(2): 74-108.
Search in Google Scholar Back to article
Boonkitticharoen V, Kulapaditharom B, Leopairut J, Kraiphibul P, Larbcharoensub N, Cheewaruangroj W, et al. Vascular endothelial growth factor a and proliferation marker in prediction of lymph node metastasis in oral and pharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2008; 134(12): 1305-1311.
Search in Google Scholar Back to article
Eleftheriadou A, Chalastras T, Ferekidou E, Yio-takis I, Kyriou L, Tzagarakis M, et al. Association between squamous cell carcinoma of the head and neck and serum folate and homocysteine. Anticancer Res. 2006; 26(3B): 2345-2348.
Search in Google Scholar Back to article
Lo AK, Lo KW, Tsao SW, Wong HL, Hui JW, To KF, et al. Epstein-Barr virus infection alters cellular signal cascades in human nasopharyngeal epithelial cells. Neoplasia. 2006; 8(3): 173-180.
Search in Google Scholar Back to article
Hennessey PT, Westra WH, Califano JA. Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. J Dent Res. 2009; 88(4): 300-306.
Search in Google Scholar Back to article
Weber BL. Cancer genomics. Cancer Cell. 2002; 1(1): 37-47.
Search in Google Scholar Back to article
Ha PK, Chang SS, Glazer CA, Califano JA, Sidran-sky D. Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol. 2009; 45(4-5): 335-339.
Search in Google Scholar Back to article
Cassidy LD, Venkitaraman AR. Genome instability mechanisms and the structure of cancer genomes. Curr Opin Genet Dev. 2012; 22(1): 10-13.
Search in Google Scholar Back to article
Viet CT, Schmidt BL. Understanding oral cancer in the genome era. Head Neck. 2010; 32(9): 1246-1268.
Search in Google Scholar Back to article
Agrawal N, Frederick MJ, Pickering CR, Bette-gowda C, Chang K, Li RJ, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011; 333(6046): 1154-1157.
Search in Google Scholar Back to article
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011; 333(6046): 1157-1160.
Search in Google Scholar Back to article
Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, et al. Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol. 2006; 24(25): 4170-4176.
Search in Google Scholar Back to article
Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005; 5(5): 341-354.
Search in Google Scholar Back to article
Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2010; 11(1): 9-22.
Search in Google Scholar Back to article
Kanai Y, Hirohashi S. Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from precancerous to malignant state. Carcinogenesis. 2007; 28(12): 2434-2442.
Search in Google Scholar Back to article
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3(6): 415-428.
Search in Google Scholar Back to article
Ushijima T. Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer. 2005; 5(3): 223-231.
Search in Google Scholar Back to article
Baylin SB, Ohm JE. Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006; 6(2): 107-116.
Search in Google Scholar Back to article
Lee S, Kim WH, Jung HY, Yang MH, Kang GH. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. Am J Pathol. 2002; 161(3): 1015-1022.
Search in Google Scholar Back to article
Hasegawa M, Nelson HH, Peters E, Ringstrom E, Posner M, Kelsey KT. Patterns of gene promoter methylation in squamous cell cancer of the head and neck. Oncogene. 2002; 21(27): 4231-4236.
Search in Google Scholar Back to article
Loyo M, Brait M, Kim MS, Ostrow KL, Jie CC, Chuang AY, et al. A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma. Int J Cancer. 2011; 128(6): 1393-1403.
Search in Google Scholar Back to article
Dikshit RP, Gillio-Tos A, Brennan P, De Marco L, Fiano V, Martinez-Peñuela JM, et al. Hypermethylation, risk factors, clinical characteristics, and survival in 235 patients with laryngeal and hypopharyngeal cancers. Cancer. 2007; 110(8): 1745-1751.
Search in Google Scholar Back to article
Poage GM, Christensen BC, Houseman EA, Mc-Clean MD, Wiencke JK, Posner MR, et al. Genetic and epigenetic somatic alterations in head and neck squamous cell carcinomas are globally coordinated but not locally targeted. PLoS One. 2010; 5(3): e9651.
Search in Google Scholar Back to article
Sanchez-Cespedes M, Esteller M, Wu L, Yoo GH, Koch WM, Jen J, et al. Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res. 2000; 60(4): 892-895.
Search in Google Scholar Back to article
Ogi K, Toyota M, Ohe-Toyota M, Tanaka N, Noguchi M, Sonoda T, et al. Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma. Clin Cancer Res. 2002; 8(10): 3164-3171.
Search in Google Scholar Back to article
Saloura V, Vougiouklakis T, Zewde M, Deng X, Kiyotani K, Park J-H, et al. WHSC1L1-mediated EGFR mono-methylation enhances the cytoplasmic and nuclear oncogenic activity of EGFR in head and neck cancer. Sci Rep. 2017; 7: 40664.
Search in Google Scholar Back to article
Liao H-W, Hsu J-M, Xia W, Wang H-L, Wang Y-N, Chang W-C, et al. PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response. J Clin Invest. 2015; 125(12): 4529-4543.
Search in Google Scholar Back to article
Stein RA. Epigenetics-the link between infectious diseases and cancer. JAMA. 2011; 305(14): 14841485.
Search in Google Scholar Back to article
Nagothu KK, Rishi AK, Jaszewski R, Kucuk O, Majumdar APN. Folic acid- mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells. Am J Physiol Gastrointest Liver Physiol. 2004; 287(3): G541-G546.
Search in Google Scholar Back to article
Langevin SM, Koestler DC, Christensen BC, Butler RA, Wiencke JK, Nelson HH, et al. Peripheral blood DNA methylation profiles are indicative of head and neck squamous cell carcinoma: An epigenome-wide association study. Epigenetics. 2012; 7(3): 291-299.
Search in Google Scholar Back to article
Rosas SL, Koch W, Costa Carvalho MG, Wu L, Califano J, Westra W, et al. Promoter hypermethylation patterns of p16 O-6-methylguanine-DNA methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res. 2001; 61(3): 939-942.
Search in Google Scholar Back to article
Nagase H, Ghosh S. Epigenetics: differential DNA methylation in mammalian somatic tissues. FEBS J. 2008; 275(8): 1617-1623.
Search in Google Scholar Back to article
Costello JF, Frushwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, et al. Aberrant CpG-island methylation has non-random and tumor-type-specific patterns. Nat Genet. 2000; 24(2): 132-138.
Search in Google Scholar Back to article
Goldenberg D, Harden S, Masayesva BG, Ha P, Benoit N, Westra WH, et al. Intraoperative molecular margin analysis in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2004; 130(1): 39-44.
Search in Google Scholar Back to article
Zvonko M, Supić G, Branković-Magić M, Jović N. DNA methylation in the pathogenesis of head and neck cancer. In: Dricu A, editor. Methylation – From DNA, RNA and Histones to Diseases and Treatment. London, UK: InTech. 2012: 185-216. doi: 10.5772/51169.
Open DOI Search in Google Scholar Back to article
Arantes LMRB, de Carvalho AC, Melendez ME, Carvalho AL, Goloni-Bertollo EM. Methylation as a biomarker for head and neck cancer. Oral Oncol. 2014; 50(6): 587-592.
Search in Google Scholar Back to article
Freedman L. Quantitative science methods for bio-marker validation in chemoprevention trials. Cancer Biomark. 2007; 3(3): 135-140.
Search in Google Scholar Back to article
Maiti GP, Mondal P, Mukherjee N, Ghosh A, Ghosh S, Dey S, et al. Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and CDC25A genes. PLoS One. 2013; 8(5): e63440.
Search in Google Scholar Back to article
de Vos L, Gevensleben H, Schröck A, Franzen A, Kristiansen G, Bootz F, et al. Comparison of quantification algorithms for circulating cell-free DNA methylation biomarkers in blood plasma from cancer patients. Clin Epigenet. 2017; 9: 125.
Search in Google Scholar Back to article
Widschwendter M, Apostolidou S, Raum E, Rothenbacher D, Fiegl H, Menon U, et al. Epigenotyping in peripheral blood cell DNA and breast cancer risk: A proof of principle study. PLoS One. 2008; 3(7): e2656.
Search in Google Scholar Back to article
Pedersen KS, Bamlet WR, Oberg AL, de Andrade M, Matsumoto ME, Tang H, et al. Leukocyte DNA meth-ylation signature differentiates pancreatic cancer patients from healthy controls. PLoS One. 2011; 6(3): 18223.
Search in Google Scholar Back to article
Marsit CJ, Koestler DC, Christensen BC, Karagas MR, Houseman EA, Kelsey KT. DNA methylation array analysis identifies profiles of blood-derived DNA methylation associated with bladder cancer. J Clin Oncol. 2011; 29(9): 1133-1139.
Search in Google Scholar Back to article
Pulling LC, Divine KK, Klinge DM, Gilliland FD, Kang T, Schwartz AG, et al. Promoter hypermethylation of the O6-methylguanine-DNA methyltransferase gene: more common in lung adenocarcinomas from never-smokers than smokers and associated with tumor progression. Cancer Res. 2003; 63(16): 4842-4848.
Search in Google Scholar Back to article
Liu Y, Lan Q, Siegfried JM, Luketich JD, Keohavong P. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia. 2006; 8(1): 46-51.
Search in Google Scholar Back to article
Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994; 7(4): 536-540.
Search in Google Scholar Back to article
Montero AJ, Diaz-Montero CM, Mao L, Youssef EM, Estecio M, Shen L, et al. Epigenetic inactivation of EGFR by CpG island hypermethylation in cancer. Cancer Biol Ther. 2006; 5(11): 1494-1501.
Search in Google Scholar Back to article

Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group

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