ArticleBMC genomics2012
LRpath analysis reveals common pathways dysregulated via DNA methylation across cancer types.
Article in BMC genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed.
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- Metabolic Alterations and WNT Signaling Impact Immune Response in HGSOC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
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- Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles.Scientific reports · 2021Article
- Capitalizing on transcriptome profiling to optimize and identify targets for promoting early murine folliculogenesis in vitro.Scientific reports · 2021Article
- The ecotoxicological contaminant tris(4-chlorophenyl)methanol (TCPMOH) impacts embryonic development in zebrafish (Danio rerio).Aquatic toxicology (Amsterdam, Netherlands) · 2021Article
- Regulation of meiotic progression by Sertoli-cell androgen signaling.Molecular biology of the cell · 2020Article
- Sensitivity to differential NRF1 gene signatures contributes to breast cancer disparities.Journal of cancer research and clinical oncology · 2020Article
- Pan-cancer analysis of differential DNA methylation patterns.BMC medical genomics · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundThe relative contribution of epigenetic mechanisms to carcinogenesis is not well understood, including the extent to which epigenetic dysregulation and somatic mutations target similar genes and pathways. We hypothesize that during carcinogenesis, certain pathways or biological gene sets are commonly dysregulated via DNA methylation across cancer types. The ability of our logistic regression-based gene set enrichment method to implicate important biological pathways in high-throughput data is well established.
resultsWe developed a web-based gene set enrichment application called LRpath with clustering functionality that allows for identification and comparison of pathway signatures across multiple studies. Here, we employed LRpath analysis to unravel the commonly altered pathways and other gene sets across ten cancer studies employing DNA methylation data profiled with the Illumina HumanMethylation27 BeadChip. We observed a surprising level of concordance in differential methylation across multiple cancer types. For example, among commonly hypomethylated groups, we identified immune-related functions, peptidase activity, and epidermis/keratinocyte development and differentiation. Commonly hypermethylated groups included homeobox and other DNA-binding genes, nervous system and embryonic development, and voltage-gated potassium channels. For many gene sets, we observed significant overlap in the specific subset of differentially methylated genes. Interestingly, fewer DNA repair genes were differentially methylated than expected by chance.
conclusionsClustering analysis performed with LRpath revealed tightly clustered concepts enriched for differential methylation. Several well-known cancer-related pathways were significantly affected, while others were depleted in differential methylation. We conclude that DNA methylation changes in cancer tend to target a subset of the known cancer pathways affected by genetic aberrations.
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