Methylation of p16 ink4a promoter is independent of human papillomavirus DNA physical state: a comparison between cervical pre-neoplastic and neoplastic samples
| Autor: | Miguel A. M. Moreira, Sergio M. Amaro-Filho, Fernanda Nahoum Carestiato, Silvia Maria Baeta Cavalcanti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine Microbiology (medical) HPV16 lcsh:Arctic medicine. Tropical medicine Adolescent cervical cancer lcsh:RC955-962 lcsh:QR1-502 Uterine Cervical Neoplasms integration Biology medicine.disease_cause Polymerase Chain Reaction lcsh:Microbiology law.invention Young Adult 03 medical and health sciences 0302 clinical medicine law Biomarkers Tumor medicine Humans Epigenetics Gene Cyclin-Dependent Kinase Inhibitor p16 Polymerase chain reaction Aged Cervical cancer Human papillomavirus 16 Papillomavirus Infections Cancer Methylation Middle Aged medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Concomitant DNA Viral Carcinoma Squamous Cell Cancer research Female Original Article methylation p16 ink4a Carcinogenesis Precancerous Conditions |
| Zdroj: | Memórias do Instituto Oswaldo Cruz., Vol 114, Iss 0 (2018) Memórias do Instituto Oswaldo Cruz Memórias do Instituto Oswaldo Cruz, Volume: 114, Article number: e180456, Published: 17 DEC 2018 |
| ISSN: | 1678-8060 |
| Popis: | BACKGROUND Epigenetic modifications in host cells, like p16 ink4a methylation, have been considered as putative complementary mechanisms for cancer development. Because only a small proportion of infected women develop cervical cancer, other factors might be involved in carcinogenesis, either independently or in association with high-risk human papillomavirus (HR-HPV) infections, including epigenetic factors. OBJECTIVES We hypothesised that p16 ink4a methylation might have a role in cancer development driven by HPV16, mainly in the presence of intact E1/E2 genes. Thus, our objectives were to assess the status of p16 ink4a methylation and the HPV16 E1/E2 integrity in samples in different stages of cervical diseases. METHODS Presence of HPV16 was determined by E6 type-specific polymerase chain reaction (PCR). Methylation status of the p16 ink4a promoter was assessed by methylation-specific PCR in 87 cervical specimens comprising 29 low-grade (LSIL), 41 high-grade (HSIL) lesions, and 17 cervical cancers (CC). Characterisation of E1 and E2 disruption (as an indirect indicator of the presence of episomal viral DNA) was performed by PCR amplifications. FINDINGS We observed a significantly increased trend (nptrend = 0.0320) in the proportion of methylated p16 ink4a in cervical samples during cancer development. Concomitant E1 and E2 disruptions were the most frequent pattern found in all groups: CC (76%), HSIL (54%), and LSIL (73%). No statistically significant differences between p16 ink4a methylation and E1/E2 integrity, in histological groups, was observed. MAIN CONCLUSIONS There was an increase in methylation of the p16 ink4a promoter from pre-neoplastic lesions to cancer. Additionally, a high frequency of E1/E2 disruptions in LSIL/HSIL suggested that viral DNA integration was an early event in cervical disease. Moreover, the methylation status was apparently independent of HPV16 integrity. |
| Databáze: | OpenAIRE |
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