Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer

Calmon, Marília Freitas; Colombo, Jucimara; Carvalho, Flávio; Souza, Fátima Pereira de; Filho, José Francisco Góis; Fukuyama, Érica Erina; Camargo, Anamaria A.; Caballero, Otávia L.; Tajara, Eloíza H.; Cordeiro, José Antônio; Rahal, Paula

doi:10.1016/j.cancergencyto.2006.09.008

Cited by 86 publications

(63 citation statements)

References 23 publications

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“…Several groups investigated the methylation profile of various genes like p16, p15, MGMT, hMLH, Ecadherin and DAP-K in oral squamous cell carcinoma [17,18]. Though currently, multiple reports have identified the correlation between some tumour-related genes such as CDKN2A/p16, DAP-K and MGMT in endometrial, endobronchial and cervical premalignant lesions [19,20] yet, no such significant correlation have been studied in oral premalignant lesion.…”

Section: Discussionmentioning

confidence: 99%

Promoter Hypermethylation Profile of Tumour Suppressor Genes in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Asokan¹,

Jeelani²,

Gnanasundaram³

2014

JCDR

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Purpose of the Study: The present study was conducted to evaluate epigenetic alteration of five tumour suppressor genes in the oral precancer and cancer patients. Materials and Methods:The study was carried out in three groups namely control group of five people (normal healthy individuals), 10 oral leukoplakia patients and 10 oral squamous cell carcinoma patients. Incisional biopsy was done and part of the tissue sent for histological examination and part of tissue sent for hypermethylation study of p16, p15, hMLH, MGMT, E-cadherin tumour suppressor genes. Methylation specific polymerase chain reaction was carried out for detecting methylation in promoter regions of tumour suppressor genes. The resultant PCR products were run in a 2.5% agarose gel and the promoter hypermethylation status of the five tumour suppressor genes were analysed. Results:In oral Leukoplakia patients, 60% of methylation in the case of p16 gene, 30% of methylation in the case of MGMT gene and 60% of methylation in the case of E-cadherin gene. In oral Squamous cell carcinoma patients, 60% of methylation in the case of p16 gene, 40% of methylation in the case of MGMT, 60% of methylation in the case of E-cadherin gene, 20% in case of p15,10% in case of hMLH gene. Conclusion:Our results suggest that epigenetic mechanisms of inactivation of tumour suppressor genes, such as aberrant methylation of p16 and E-cadherin genes occur early in head and neck tumourigenesis and might play a role in the progression of these lesions.

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Section: Discussionmentioning

confidence: 99%

Promoter Hypermethylation Profile of Tumour Suppressor Genes in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Asokan¹,

Jeelani²,

Gnanasundaram³

2014

JCDR

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“…E-cadherin expression is similar between primary tumors and metastases, perhaps because of MET in metastatic tumors. The promoter region of the E-cadherin gene (CDH1) is hypermethylated in HNSCC, but hypermethylation is not correlated with advanced stage (Calmon et al, 2007), mortality, or second primary tumor (Dikshit et al, 2007). Metaanalysis of E-cadherin studies in HNSCC showed that abnormal E-cadherin expression is predictive of diminished diseasespecific survival (Zhao et al, 2012).…”

Section: Biomarkers Of Epithelialmesenchymal Transition In Squamous Cmentioning

confidence: 99%

Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

et al. 2012

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An understanding of the process by which tumor cells destroy the basement membrane of the surface epithelium, invade, and metastasize is essential to the development of novel treatment of head and neck squamous cell carcinoma (HNSCC). In recent years, there has been increased interest in the role of epithelial-mesenchymal transition (EMT) in invasion. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. There are 3 known types of EMT that mediate development, wound healing, and carcinogenesis. This review summarizes studies of known EMT biomarkers in the context of HNSCC progression. The biomarkers discussed come from a wide range of proteins, including cell-surface proteins (E-cadherin, N-cadherin, and Integrins), cytoskeletal proteins (α-Smooth Muscle Actin, Vimentin, and β-catenin), extracellular matrix proteins (Collagens, Fibronectin, and Laminin), and transcription factors (SNAIL1, SNAIL2, TWIST, and LEF-1). Overall, the findings of these studies suggest that EMT mediates HNSCC progression. The mechanistic role of the EMT markers that have been associated with HNSCC should be more clearly defined if new anti-HNSCC therapies to block EMT progression are to be developed.KEY WORDS: disease progression, extracellular matrix, oral pathology, neoplasm invasiveness, biological markers, head and neck neoplasms.

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“…Analysis of ADAM23 binding to integrins has revealed a specific interaction with a v h 3 mediated by the disintegrin domain (22). The ADAM23 gene is frequently silenced in breast (23), gastric (24), pancreatic (25), and head and neck (26) tumors as well as in gliomas (27). In breast tumors, we showed that the ADAM23 gene is frequently silenced by promoter hypermethylation and that primary breast tumors in more advanced stages show a higher degree of DNA methylation, suggesting that silencing of ADAM23 might be associated with the acquisition of a metastatic phenotype (23).…”

Section: Introductionmentioning

confidence: 99%

ADAM23 Negatively Modulates αvβ3 Integrin Activation during Metastasis

Verbisck

Costa

et al. 2009

Cancer Research

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The ADAM23 gene is frequently silenced in different types of tumors, and, in breast tumors, silencing is correlated with tumor progression, suggesting that it might be associated with the acquisition of a metastatic phenotype. ADAM23 exerts its function mainly through the disintegrin domain, because its metalloprotease domain is inactive. Analysis of ADAM23 binding to integrins has revealed a specific interaction with A v B 3 integrin mediated by the disintegrin domain. Altered expression of A v B 3 integrin has been observed in different types of tumors, and expression of this integrin in the activated form has been shown to promote metastasis formation. Here, we investigated the possibility that interaction between ADAM23 and A v B 3 integrin might negatively modulate A v B 3 activation during metastatic progression. ADAM23 expression was knocked down using short hairpin RNA in the MDA-MB-435 cell line, which has been extensively used as a model for A v B 3 integrin activation. Ablation of ADAM23 enhanced A v B 3 integrin activation by at least 2-to 4-fold and ADAM23 knockdown cells showed enhanced migration and adhesion to classic A v B 3 integrin ligands. Ablation of ADAM23 expression also enhanced pulmonary tumor cell arrest in immunodeficient mice. To complement our findings with clinical evidence, we showed that silencing of ADAM23 gene by DNA promoter hypermethylation in a collection of 94 primary breast tumors was significantly associated with lower distant metastases-free and disease-specific survivals and was an independent prognostic factor for poor disease outcome. Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating A v B 3 integrin activation. [Cancer Res 2009;69(13):5546-52]

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Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer

Cited by 86 publications

References 23 publications

Promoter Hypermethylation Profile of Tumour Suppressor Genes in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Promoter Hypermethylation Profile of Tumour Suppressor Genes in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma

ADAM23 Negatively Modulates αvβ3 Integrin Activation during Metastasis

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