ArticleOncotarget2016
Distinct features between MLH1-methylated and unmethylated colorectal carcinomas with the CpG island methylator phenotype: implications in the serrated neoplasia pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
The trial behind it
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
25 citing papers in PubMed, 40 citations in OpenAlex.
- Distinct Clinical Characteristics and Predictors of Sporadic Mismatch Repair-Deficient Colorectal Cancer.Gastro hep advances · 2025Review
- Immune microenvironmental heterogeneity according to tumor DNA methylation phenotypes in microsatellite instability-high colorectal cancers.Cancer immunology, immunotherapy : CII · 2024Article
- The utility of liquid biopsy-based methylation biomarkers for colorectal cancer detection.Frontiers in oncology · 2024Article
- Article
- Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis.International journal of molecular sciences · 2022Review
- Article
- What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?World journal of gastroenterology · 2020Review
- Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values.Pathology oncology research : POR · 2020Article
- Evolving pathologic concepts of serrated lesions of the colorectum.Journal of pathology and translational medicine · 2020Review
- Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies.Journal for immunotherapy of cancer · 2020Review
- CpG Island Methylation in Sessile Serrated Adenoma/Polyp of the Colorectum: Implications for Differential Diagnosis of Molecularly High-Risk Lesions among Non-dysplastic Sessile Serrated Adenomas/Polyps.Journal of pathology and translational medicine · 2019Article
- Article
- Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives.Clinical advances in hematology & oncology : H&O · 2018Review
- Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer.Cancers · 2018Article
- Strategy to targeting the immune resistance and novel therapy in colorectal cancer.Cancer medicine · 2018Review
- Single nucleotide polymorphisms inOncotarget · 2017Article
- Overexpression of POSTN in Tumor Stroma Is a Poor Prognostic Indicator of Colorectal Cancer.Journal of pathology and translational medicine · 2017Article
- Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.British journal of cancer · 2017Article
- Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.International journal of molecular sciences · 2017Article
- What influences preneoplastic colorectal lesion recurrence?Oncotarget · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presence or absence of MLH1 methylation may critically affect the heterogeneity of colorectal carcinoma (CRC) with the CpG island methylator phenotype (CIMP). Here, we investigated the differential characteristics of CIMP-high (CIMP-H) CRCs according to MLH1 methylation status. To further confirm the MLH1-dependent features in CIMP-H CRC, an independent analysis was performed using data from The Cancer Genome Atlas (TCGA). In our CIMP-H CRC samples, MLH1-methylated tumors were characterized by older patient age, proximal colonic location, mucinous histology, intense lymphoid reactions, RUNX3/SOCS1 promoter methylation, BRAF mutations, and microsatellite instability-high (MSI-H) status. By contrast, MLH1-unmethylated tumors were associated with earlier age of onset, increased distal colorectal localization, adverse pathologic features, and KRAS mutations. In the TCGA dataset, the MLH1-silenced CIMP-H CRC demonstrated proximal location, MSI-H status, hypermutated phenotype, and frequent BRAF mutations, but the MLH1-non-silenced CIMP-H CRC was significantly associated with high frequencies of KRAS and APC mutations. In conclusion, the differential nature of CIMP-H CRCs depends primarily on the MLH1 methylation status. Based on the current knowledge, the sessile serrated adenoma/polyp may be the major precursor of MLH1-methylated CIMP-H CRCs, whereas MLH1-unmethylated CIMP-H CRCs may develop predominantly from KRAS-mutated traditional serrated adenomas and less commonly from BRAF-mutated traditional serrated adenomas and/or sessile serrated adenomas/polyps.
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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.