Methylation of P16, P21, P27, RB1 and P53 genes in odontogenic keratocysts

Moreira, Paula Rocha; Guimarães, Mariana Moreira; Guimarães, André Luiz Sena; Diniz, Marina Gonçalves; Gomes, Carolina Cavaliéri; Brito, João Artur Ricieri; Gomez, Ricardo Santiago

doi:10.1111/j.1600-0714.2008.00718.x

Cited by 58 publications

(53 citation statements)

References 33 publications

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“…Genetic and epigenetic factors are associated with a susceptibility to cancer development at a young age (4,37). Alternatively, genetic and epigenetics factors may play a stronger role than HPV-16/18 infection in the development of HNSSC at an early age (38)(39)(40)(41)(42). In the current study, we did not observe differences in survival associated with age, in agreement with previous studies (4,37).…”

Section: Discussionsupporting

confidence: 82%

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

et al. 2012

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Abstract.Recently, high-risk human papillomavirus (HPV) has emerged as a possible agent associated with head and neck squamous cell carcinoma (HNSCC) in younger patients. Therefore, the purpose of the present study was to assess the effect of age on the distribution of HPV-16/18 in HNSCC, together with the impact of the virus on patient prognosis. A longitudinal prospective study was used adjusted for age, gender, TNM staging, smoking status and alcohol consumption. HPV was detected by PCR with consensus primers. Results showed there was no difference in the frequency of HPV-16/18 positivity when younger patients were compared to the older patients. No association was found among highrisk HPV positivity, gender, smoking habit and anatomical site. High-risk HPV was associated with advanced TNM in bivariate analyses; however, it did not impact on survival. Only TNM staging was associated with risk of mortality. Our study supports the theory that age does not affect the presence of HPV-16/18 in HNSCC and has no impact on patient prognosis. The incidence of HNSCC among patients under the age of 45 years is reportedly on the increase worldwide. The factors associated with HNSCC in younger adults are not well established. Findings of this study indicate that HPV-16/18 may not play a role in HNSCC patients under the age of 45 years.

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Section: Discussionsupporting

confidence: 82%

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

et al. 2012

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“…The p16 CDKN2A gene methylation profile was evaluated by using methylation-specific PCR (MSP). DNA samples were treated with bisulfite for 3 h, and MSP-PCR was performed as described previously [33] and later modified [34] . The p16 CDKN2A promoter was defined as methylated or unmethylated on the basis of 2 distinct PCR reactions that yielded fragment sizes of 150 and 151 bp, respectively.…”

Section: Dna Isolation and Bisulfite Conversion Of Dna Formentioning

confidence: 99%

Analysis of p16CDKN2A Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

Fonseca–Silva¹,

Farias²,

Cardoso

et al. 2012

Pathobiology

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Objective: The purpose of this study was to investigate the relationship between p16_CDKN2A methylation and epithelial dysplasia (ED). We also evaluated the expressions of proteins related to methylation (DNMT3B and DNMT1). Finally, we tested whether HPV-16/18 or the dmt3b (C46359T) polymorphism is associated with p16_CDKN2A methylation status. Methods: To test the hypothesis, a case-control study with 72 (control, n = 24; ED, n = 48) tissue samples from subjects was performed. Methylation-specific PCR, RFLP, and immunohistochemical analyses were performed to evaluate p16_CDKN2A methylation status, dmt3b (C46359T) genotyping, and protein levels, respectively. Results: The methylation of p16_CDKN2A and HPV-16 was associated with ED gradation (p = 0.001 and 0.002, respectively). In addition, most HPV-16-positive samples (77.8%) exhibited p16_CDKN2A methylation; however, changes in DNMT3B and DNMT1 protein levels were not observed in HPV-positive samples. Neither HPV-18 nor the dmt3b polymorphism was associated with p16_CDKN2A methylation. Conclusions: There is an association between the presence of HPV-16 in ED and the occurrence of p16_CDKN2A methylation. Both variables are also associated with ED development, but further studies are necessary to clarify if they operate independently and if they have any impact on OD malignization.

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“…The presence or absence of methyl groups in cytosines promotes the remodeling of chromatin, making it less or more accessible to transcription (5). Epigenetic alterations related to the regulation of genes involved in the cell cycle control have been described in different benign and malignant neoplasms (6)(7)(8). Recently, distinct methylation profiles in tumor suppressor genes have been reported in epithelial odontogenic tumors (9).…”

Section: Hypomethylation Of Tumor Suppressor Genes In Odontogenic Myxomamentioning

confidence: 99%

“…Primer sequences and amplification conditions used to evaluate P16, P21, P27, P53, and RB1 genes were previously reported (8,(11)(12)(13). The reactions were performed in a thermocycler (Eppendorf AG, Hamburg, Germany), and the PCR products were visualized in silver-stained 6.5% polyacrylamide gel.…”

Section: Methylation-specific Pcr (Msp-pcr)mentioning

confidence: 99%

Hypomethylation of tumor suppressor genes in odontogenic myxoma

et al. 2011

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Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

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Methylation of P16, P21, P27, RB1 and P53 genes in odontogenic keratocysts

Abstract: Our data show methylation of the promoter of P21 gene in OKCs. In addition, methylation of the P27 and RB1 genes are commonly found in dental follicles. Further studies are necessary to determine the functional relevance of these alterations.

Cited by 58 publications

References 33 publications

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

Analysis of p16<sub><i>CDKN2A</i></sub> Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

Hypomethylation of tumor suppressor genes in odontogenic myxoma

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