Global analysis of DNA methylation changes during progression of oral tumorigenesis

ABSTRACT: Objectives: Earlier studies involving a priori gene selection have identified promoter regions deregulated by DNA methylation changes in oral squamous cell cancers (OSCCs) and precancers. Interrogation of global DNA methylation patterns for such specimens has not been reported, though such analyses are needed to uncover novel molecular factors driving disease. Materials and Methods: We evaluated global DNA methylation patterns for 30 biopsies obtained from 10 patients undergoing surgical removal of an OSCC or carcinoma in situ (CIS). From a disease field in each patient, we collected i) dysplastic, ii) CIS or OSCC, and iii) adjacent normal biopsies. DNA isolated from each biopsy was profiled for methylation status using the Illumina HumanMethylation27K platform. Results: Our data demonstrate that aberrant methylation of promoter CpG islands exists across oral precancer and OSCC genomes. Non-hierarchical clustering of all methylation data revealed distinct methylation patterns between the normal and the CIS/OSCC tissues (with results for dysplastic biopsies split between groups). Multiple genes exhibiting recurrent aberrant DNA methylation were found for both dysplastic and CIS/OSCC groups, and included enrichment for genes found in the WNT and MAPK signaling pathways. Conclusion: In identifying aberrant DNA methylation at the earliest stages of oral precancer and finding recurring epigenetic disruption of specific genes/pathways across our analyzed cohort, we conclude that CpG methylation changes are a hallmark of oral cancer progression and that global DNA methylation analyses are an essential component for wider studies seeking to derive biomarkers or potentially druggable targets for improving oral cancer outcomes. Bisulphite converted DNA from the 30 samples were hybridised to the Illumina Infinium 27k Human Methylation BeadChip v1.2. Total RNA from 30 oral cancer samples were hybridized to Agilent 4x44k gene expression microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: Towle Rebecca 

PROVIDER: S-ECPF-GEOD-46802 | biostudies-other |

REPOSITORIES: biostudies-other