DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes
Abstract
AIM: The onset and progression of colorectal cancer (CRC) involves a cascade of genetic and/or epigenetic events. The aim of the present study was to address the DNA methylation status of genes relevant in colorectal carcinogenesis and its progression, such as genes frequently mutated in CRC, genes involved in the DNA repair and Wnt signaling pathway. MATERIAL & METHODS: We analyzed methylation status in totally 160 genes in 12 paired colorectal tumors and adjacent healthy mucosal tissues using the Illumina Infinium Human Methylation 450 BeadChip. RESULTS: We found significantly aberrant methylation in 23 genes (NEIL1, NEIL3, DCLRE1C, NHEJ1, GTF2H5, CCNH, CTNNB1, DKK2, DKK3, FZD5 LRP5, TLE3, WNT2, WNT3A, WNT6, TCF7L1, CASP8, EDNRB1, GPC6, KIAA1804, MYO1B, SMAD2 and TTN). External validation by mRNA expression showed a good agreement between hypermethylation in cancer and down-regulated mRNA expression of the genes EDNRB1, GPC6 and SMAD2, and between hypomethylation and up-regulated mRNA expression of the CASP8 and DCLRE1C genes. CONCLUSION: Aberrant methylation of the DCLRE1C and GPC6 genes are presented here for the first time and are therefore of special interest for further validation as novel candidate biomarker genes in CRC, and merit further validation with specific assays.
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Alterations in DNA methylation have been identified in genes that are frequently mutated in CRC and in genes involved in DNA repair and the Wnt/β-catenin pathway.
“Alterations in DNA methylation have been identified in genes that are frequently mutated in CRC and in genes involved in DNA repair and the Wnt/β-catenin pathway [24].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [24]
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- Authors
- Farkas, S. A., Vymetalkova, V., Vodickova, L., Vodicka, P., & Nilsson, T. K.
- Affiliations
- Örebro University (SE)
- Czech Academy of Sciences (CZ)
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14200Prague, Czech Republic
- Umeå University (SE)
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2014-04
- Volume
- 6
- Issue
- 2
- Pages
- 179-191
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- OpenAlex
- W2139296757
- Cited by
- 67
- References
- 52
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 6
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epigenomics (publishedVersion)
- PubMed (publishedVersion)
- ASEP (submittedVersion, public-domain)
- Funders
- y CZ:GA CR GA (P304/11/P715, P304/12/1585)
- IGA:NT (14329)
- Lions Cancer Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- colorectal cancer, DNA methylation, sporadic colorectal cancer, DNA repair genes, Wnt/β-catenin signaling, gene hypermethylation, gene hypomethylation, DCLRE1C, GPC6, Smad2, CTNNB1, candidate biomarkers, colorectal carcinogenesis, mRNA expression
- MeSH terms
- Aged, DNA Repair, DNA-Binding Proteins, Endonucleases, Female, Humans, Male, Middle Aged, Nuclear Proteins, Promoter Regions, Genetic, RNA, Messenger, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, CpG Islands, DNA Methylation, Epigenesis, Genetic, Wnt Proteins, beta Catenin, Glypicans, Wnt Signaling Pathway
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