hrvatski jezikClear Cookie - decide language by browser settings

Methylated Host Cell Gene Promoters and Human Papillomavirus Type 16 and 18 Predicting Cervical Lesions and Cancer

Milutin Gašperov, Nina; Sabol, Ivan; Planinić, Pavao; Grubišić, Goran; Fistonić, Ivan; Ćorušić, Ante; Grce, Magdalena (2015) Methylated Host Cell Gene Promoters and Human Papillomavirus Type 16 and 18 Predicting Cervical Lesions and Cancer. PLoS One, 10 (6). e0129452-1. ISSN 1932-6203

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (490kB) | Preview
[img]
Preview
PDF - Accepted Version
Available under License Creative Commons Attribution.

Download (563kB) | Preview

Abstract

Change in the host and/or human papillomavirus (HPV) DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP). The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5’LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters’ methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.

Item Type: Article
Uncontrolled Keywords: aberrant dna methylation; intraepithelial neoplasia; cpg methylation; candidate biomarker; hpv infection; l1 gene; progression; lines; patterns; genome
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Promijenjeno stanje DNA-metilacije u HPV-povezanim oštećenjima[138731] Magdalena Grce098-0982464-2510MZOS
Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and DevelopmentOliver Vugrek316289FP7
Depositing User: Magdalena Grce
Date Deposited: 13 Aug 2015 13:36
Last Modified: 23 Nov 2015 11:48
URI: http://fulir.irb.hr/id/eprint/2094
DOI: 10.1371/journal.pone.0129452

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year