Gene hypermethylation in tumor tissue of advanced oral squamous cell carcinoma patients

Šupić, Gordana; Kozomara, Ružica; Branković-Magić, Mirjana; Jović, N; Magić, Zvonko

doi:10.1016/j.oraloncology.2009.07.007

Cited by 69 publications

(35 citation statements)

References 38 publications

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“…The WS gene WRN is mutated in patients with this syndrome and plays roles in telomere maintenance, DNA repair, and transcription. 57 WRN has been shown to be aberrantly methylated in disease, such as advanced oral squamous cell carcinoma 58 ; however, no studies have comprehensively investigated the methylome of WS patients. It would be interesting to know if these patients display atypical DNMT expression as well as atypical DNA methylation patterns compared to healthy controls.…”

Section: Dna Hypomethylation and Hypermethylationmentioning

confidence: 99%

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Johnson

Akman²,

Calimport³

et al. 2012

Rejuvenation Research

317

218

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DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

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Section: Dna Hypomethylation and Hypermethylationmentioning

confidence: 99%

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Johnson

Akman²,

Calimport³

et al. 2012

Rejuvenation Research

317

218

View full text Add to dashboard Cite

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“…Epigenetic silencing down-regulates a gene through DNA methylation at CpG sites in the promoter region, and has been shown to participate in the development of various types of human tumors, including HNSCC (Herman and Baylin, 2003;Ha and Califano, 2006;Supić et al, 2009). Aberrant promoter methylation may affect genes involved in cell-cycle control (P16, Rb), DNA repair (MGMT and hMLH1), cell adhesion (H-cadherin and CDH-1), apoptosis (DAPK), and cell differentiation (RARB2) (Miao et al, 2015;Xu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

et al. 2016

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ABSTRACT. Head and neck squamous cell carcinoma (HNSCC) has become one of the most common forms of cancer worldwide. Hypermethylation-induced silencing of tumor-associated gene has been proposed as an important cofactor in cancer pathology. This paper aimed to characterize the gene methylation patterns in human papillomavirus (HPV) associated-HNSCC. TIMP3 and APC methylation status in neoplastic (N = 92) and non-neoplastic tissues (N = 92) of HNSCC as well as their association with HPV infection were investigated via methylation-specific PCR assays. Results indicated that methylation level of TIMP3 was markedly higher in HPV-positive tumors as compared with HPV-negative tumors. Both TIMP3 and APC methylation were associated with lymph node metastasis and higher clinical stage of tumors. Patients with methylation at TIMP3 or APC had worse prognoses as compared to those without these alterations. This is the first study that shows a possible linkage between HPV infection and APC methylation. Methylation patterns of tumor-related genes may contribute to different disease prognosis in HNSCC according to the HPV infection status.

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“…40 In OOSCC, several studies assessing MGMT methylation using various techniques did not find associations with N status. 41,42 However, in a large study of >200 laryngeal and hypopharyngeal tumors, MGMT methylation was significantly associated with N0 status. 43 In that study, the same primers were used and a comparable MGMT methylation rate of 27% was found (also 27% in our study).…”

Section: Discussionmentioning

confidence: 99%

“…Four genes (MLH1, MGMT, CDKN2A, and DAPK1) were included that showed frequent methylation in HNSCC in the literature 41,43,56,57 (Fig. 1).…”

Section: Selection Of Candidate Genesmentioning

confidence: 99%

Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

et al. 2015

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Keywords: biomarker, DAPK1, expression, head and neck cancer, lymph node metastasis, methylation, MGMT, oral cancer Abbreviations: FFPE, formalin-fixed paraffin-embedded; OOSCC, oral and oropharyngeal squamous cell carcinoma; pN status, pathologically determined nodal status; (Q)MSP, (quantitative) methylation-specific PCR.Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pNC status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed.

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Gene hypermethylation in tumor tissue of advanced oral squamous cell carcinoma patients

Cited by 69 publications

References 38 publications

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

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