title: 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.
authors.affiliation: Department of Laboratory Medicine; Örebro University Hospital; Örebro, Sweden.
authors.forename: Sanja A
authors.initials: SA
authors.lastname: Farkas
authors.affiliation: Department of Molecular Medicine; Rudjer Boskovic Institute; Zagreb, Croatia.
authors.forename: Nina
authors.initials: N
authors.lastname: Milutin-Gašperov
authors.affiliation: Department of Molecular Medicine; Rudjer Boskovic Institute; Zagreb, Croatia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grce
authors.affiliation: Department of Laboratory Medicine; Örebro University Hospital; Örebro, Sweden; School of Health and Medical Sciences; Örebro University; Örebro, Sweden.
authors.forename: Torbjörn K
authors.initials: TK
authors.lastname: Nilsson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human; D006801:Humans; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA methylation; HPV; Infinium Human Methylation 450 BeadChip; cervical cancer; immune system