ArticleGastroenterology2008
Mutations in both KRAS and BRAF may contribute to the methylator phenotype in colon cancer.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Relationship Between Human mutL Homolog 1 (hMLH1) Hypermethylation and Colorectal Cancer: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2017Pooled it
- Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review.Clinical epigenetics · 2016Pooled it
- Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009Trial
- Biological Resectability in Colorectal Liver Metastases: A Nomogram-Based Continuous Risk Model to Define Borderline Disease.Annals of gastroenterological surgery · 2026Article
- Prognostic and clinicopathological implications of mismatch-repair deficiency and MLH1 promoter methylation status in endometrial carcinoma.International journal of clinical oncology · 2026Article
- Circulating cell-free DNA methylation patterns as non-invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles.Molecular cancer · 2024Article
- Fusobacterium nucleatum Load Correlates with KRAS Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma.Cancer research communications · 2023Article
- FILIP1L Loss Is a Driver of Aggressive Mucinous Colorectal Adenocarcinoma and Mediates Cytokinesis Defects through PFDN1.Cancer research · 2021Article
- Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations.Clinical epigenetics · 2021Article
- Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions.PloS one · 2021Article
- Article
- What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?World journal of gastroenterology · 2020Review
- Upregulation of microRNA-31 is associated with poor prognosis in patients with advanced colorectal cancer.Oncology letters · 2020Article
- DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation.iScience · 2020Article
- Promoter Hypermethylation of CHODL Contributes to Carcinogenesis and Indicates Poor Survival in Patients with Early-stage Colorectal Cancer.Journal of Cancer · 2020Article
- Integrative analysis identifies DNMTs against immune-infiltrating neutrophils and dendritic cells in colorectal cancer.Epigenetics · 2019Article
- Integrative Genome-Scale DNA Methylation Analysis of a Large and Unselected Cohort Reveals 5 Distinct Subtypes of Colorectal Adenocarcinomas.Cellular and molecular gastroenterology and hepatology · 2019Article
- Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles.Oncotarget · 2018Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsColorectal cancers (CRCs) with the CpG island methylator phenotype (CIMP) often associate with epigenetic silencing of hMLH1 and an activating mutation in the BRAF gene. However, the current CIMP criteria are ambiguous and often result in an underestimation of CIMP frequencies in CRCs. Because BRAF and KRAS belong to same signaling pathway, we hypothesized that not only mutations in BRAF but mutant KRAS may also associate with CIMP in CRC.
methodsWe determined the methylation status in a panel of 14 markers (7 canonical CIMP-related loci and 7 new loci), microsatellite instability status, and BRAF/KRAS mutations in a collection of 487 colorectal tissues that included both sporadic and Lynch syndrome patients.
resultsMethylation analysis of 7 CIMP-related markers revealed that the mean number of methylated loci was highest in BRAF-mutated CRCs (3.6) vs KRAS-mutated (1.2, P < .0001) or BRAF/KRAS wild-type tumors (0.7, P < .0001). However, analyses with 7 additional markers showed that the mean number of methylated loci in BRAF mutant tumors (4.4) was the same as in KRAS mutant CRCs (4.3, P = .8610). Although sporadic microsatellite instability high tumors had the highest average number of methylated markers (8.4), surprisingly, Lynch syndrome CRCs also demonstrated frequent methylation (5.1).
conclusionsCIMP in CRC may result from activating mutations in either BRAF or KRAS, and the inclusion of additional methylation markers that correlate with mutant KRAS may help clarify CIMP in future studies. Additionally, aberrant DNA methylation is a common event not only in sporadic CRC but also in Lynch syndrome CRCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.