Genome-wide DNA methylation assay reveals novel candidate biomarker genes in cervical cancer

Abstract

The oncogenic human papilloma viruses (HPVs) are associated with precancerous cervical lesions and development of cervical cancer. The DNA methylation signatures of the host genome in normal, precancerous and cervical cancer tissue may indicate tissue-specific perturbation in carcinogenesis. The aim of this study was to identify new candidate genes that are differentially methylated in squamous cell carcinoma compared with DNA samples from cervical intraepithelial neoplasia grade 3 (CIN3) and normal cervical scrapes. The Illumina Infinium HumanMethylation450 BeadChip method identifies genome-wide DNA methylation changes in CpG islands, CpG shores and shelves. Our findings showed an extensive differential methylation signature in cervical cancer compared with the CIN3 or normal cervical tissues. The identified candidate biomarker genes for cervical cancer represent several types of mechanisms in the cellular machinery that are epigenetically deregulated by hypermethylation, such as membrane receptors, intracellular signaling and gene transcription. The results also confirm extensive hypomethylation of genes in the immune system in cancer tissues. These insights into the functional role of DNA methylome alterations in cervical cancer could be clinically applicable in diagnostics and prognostics, and may guide the development of new epigenetic therapies.

Novel identification of biofluids using a multiplex methylation sensitive restriction enzyme-PCR system

“…This included: 20 cervical tissues from GSE46306 [31]; 17 and 5 saliva samples from GSE39560 and GSE48472 respectively [32,33]; 5 and 6 venous blood samples from GSE48472 and GSE35069 respectively [33,34]; and 8 sperm samples from GSE47627 [35]. For each CpG locus in the Infinium HumanMethylation450 BeadChip Kit, mean and standard deviation of the beta-values (the calibration ratio of methylation) for each biofluid or tissue were calculated using Microsoft Office Excel 2007.…”

Differential gene methylation in paired glioblastomas suggests a role of immune response pathways in tumor progression

“…Accordingly, it is well established that IDH1/IDH2 mutations will induce a glioma CpG island hypermethylator phenotype (G-CIMP) and this phenotype is preserved throughout glioma progression [6,10]. The role of methylation changes have been associated with tumor progression in different types of cancer [27][28][29]. In GBM, the presence of hypermethylation of tumor suppressors (RB1, EMP3, RASSF1A and BLU), cell cycle regulators (CDKN2A), DNA repair genes (MGMT, MLH1), and genes involved in tumor invasion and apoptosis (DAPK, TIMP3 and CDH1) is frequent [30][31][32][33][34][35].…”

Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population

“…ZNF582 was found to be hypermethylated in HSIL lesions and cervical cancer samples, after validation in an independent cohort. 38 These studies have demonstrated that global DNA methylation assays, like MeDIP-arrays, are powerful tools for the genomewide study of methylated genes in cervical cancer. The fact that we did not find any correlation between the candidate genes reported by these studies and the ones we are reporting may be due to differences in sample source, sample collection, microarray kinetics, bioinformatics pipelines, genetic and/or cultural factors, all of which can affect the end results of these complex experiments.…”