Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer


ABSTRACT: We performed integrative methylation, gene dosage and expression profiling to explore the interplay between promoter methylation and loss in gene silencing at 3p11-p14 in cervical cancer. Totally 26 hypermethylated genes were identified by comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue. Candidate methylation regulated genes in tumors were proposed from the correlation between methylation and gene expression. Integrated analysis of methylation, gene dosage and expression revealed three significant regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern, a gene dosage driven pattern, and a combined methylation and gene dosage driven pattern. For the LRIG1 gene, patients with both hypermethylation and loss had a worse outcome compared to those harboring only hypermethylation or none of the events. C3orf14 emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. Methylation levels from Illumina 450K methylation arrays were correlated with Illumina gene expression data in cohort 1 and validated in cohort 2.

ORGANISM(S): Homo sapiens

SUBMITTER: Heidi Lyng 

PROVIDER: E-GEOD-68339 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer.

Lando Malin M   Fjeldbo Christina S CS   Wilting Saskia M SM   C Snoek Barbara B   Aarnes Eva-Katrine EK   Forsberg Malin F MF   Kristensen Gunnar B GB   Steenbergen Renske Dm RD   Lyng Heidi H  

Epigenetics 20150101 10


Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute  ...[more]

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