Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa

Paluszczak, Jarosław; Misiak, Paulina; Wierzbicka, Małgorzata; Woźniak, Aldona; Baer‐Dubowska, Wanda

doi:10.1016/j.oraloncology.2010.11.006

Cited by 50 publications

(39 citation statements)

References 29 publications

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“…Promoter region hypermethylation-induced MGMT gene silencing has been reported in glioblastoma multiforme, head, and neck squamous cell carcinomas in general, and also specifically in oral cavity cancer [17, 42, 63, 64]. Significant downregulation of p16 gene expression due to promoter hypermethylation has been reported in colorectal cancer and oral cancer [65, 66].…”

Section: Discussionmentioning

confidence: 99%

Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

Bhatia

Goel

Makker

et al. 2014

BioMed Research International

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Promoter methylation and relative gene expression of O6-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.

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Section: Discussionmentioning

confidence: 99%

Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

Bhatia

Goel

Makker

et al. 2014

BioMed Research International

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“…Tanaka et al [49] found that methylation of the 5′ CpG island is an important mechanism for the inactivation of the FHIT gene in esophageal carcinoma. Hypermethylation of FHIT was relatively often found in oral cancer (27 %) [18] and in laryngeal carcinoma (26 %) [50]. However, it did not correlate with clinicopathological data and survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors in oral and oropharyngeal cancer based on ultrastructural analysis and DNA methylation of the tumor and surgical margin

et al. 2014

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Oral and oropharyngeal cancers are characterized by relatively low 5- year survival rates due to many factors, including local recurrence. The identification of new molecular markers may serve for the estimation of prognosis and thus augment treatment decisions and affect therapy outcome. The aim of this study was to describe the morphological characteristics and the DNA methylation status of the CDKN2A,CDH1, ATM, FHIT and RAR- genes in the central and peripheral part of the tumor and the surgical margin and evaluate their prognostic significance. 53 patients with oral and oropharyngeal cancer were enrolled to the prospective study, and had been primarily treated surgically. Correlations between morphological data, hypermethylation status and clinicopathological data, as well as prognosis, were assessed. Nuclei polymorphism highly correlated with T stage (p < 0.0001), N stage (p < 0.046), and metastases to the lymph nodes pN (p < 0.004 ). Also, the number of cells in irregular mitosis correlated with T stage (p < 0.004), and highly with pN (p < 0.009). The significance of CDKN2A hypermethylation as a good prognostic factor was also established in the Kaplan-Meir test. The ultrastructural analysis showed that none of the examined tumors had homogenous texture and that resection margin specimens clean in HE stained tissue samples frequently contained single tumor cells or few cells in groups surrounded by connective tissue. This indicates the superiority of electron microscopy over standard histopathological analysis. Thus, a combination of such morphological examination with epigenetic parameters described herein could result in the discovery of promising new prognostic markers of the disease.

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“…Improper methylation status of the following genes has been identified thus far in laryngeal cancer: Retinoic acid receptor β (RARβ), death-associated protein kinase (DAPK), cyclin-dependent kinase inhibitor 2A (CDKN2A), MGMT, RASSF1A, fragile histidine triad, chromodomain-helicase-DNA-binding protein 5, cellular retinol binding protein 1 and HIC1 (12)(13)(14)(15)(16)(17)(18)(19). The majority of the studies reported certain correlations between the clinical course of the disease and the molecular changes identified.…”

Section: Discussionmentioning

confidence: 99%

“…Kong et al (14) suggested that the hypermethylation of DAPK was associated with lymph node involvement. In addition, nodal metastases appear to correlate with the methylation profile of MGMT (15). According to Smigiel et al (17), CDKN2A hypermethylation is reflected by a high grade of histological differentiation of the tumor (G3) (17).…”

Section: Discussionmentioning

confidence: 99%

Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma

et al. 2015

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Abstract. Hypermethylated in cancer 1 (HIC1) is a putative suppressor gene, cooperating with TP53 in the regulation of apoptosis. The promoter site of this gene contains CpG islands susceptible to methylation. Altered methylation leads to the silencing of HIC1. Persistent loss of HIC1 function reflects the attenuation of proapoptotic characteristics of TP53 and may constitute the background for carcinogenesis. Altered methylation profiles along with diminished expression of HIC1 were documented in a number of solid neoplasms. The aim of this study was to evaluate the expression of the HIC1 gene in laryngeal carcinoma. RNA was extracted from samples of laryngeal cancer and corresponding healthy tissues of 21 patients with advanced laryngeal cancer (T3-T4). The amount of RNA (cDNA) was evaluated using reverse transcription-quantitative polymerase chain reaction with GADPH as the reference gene. Data demonstrated that HIC1 expression was significantly reduced in laryngeal cancer tissues. The relative expression of HIC1 was found to be ~40% lower in tumor samples compared to that in healthy controls. The median tumor/normal tissue ratio for HIC1 was 0.615. These results suggest that low HIC1 expression may be associated with neoplastic transformation in the larynx.

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Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa

Cited by 50 publications

References 29 publications

Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

Promoter Region Hypermethylation and mRNA Expression ofMGMTandp16Genes in Tissue and Blood Samples of Human Premalignant Oral Lesions and Oral Squamous Cell Carcinoma

Prognostic factors in oral and oropharyngeal cancer based on ultrastructural analysis and DNA methylation of the tumor and surgical margin

Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma

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