ArticlePloS one2015
Molecular subtypes in stage II-III colon cancer defined by genomic instability: early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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19 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
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- BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center's experience.Frontiers in oncology · 2024Article
- High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I-III Colon Cancer.Cancers · 2023Article
- Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.International journal of molecular sciences · 2022Article
- AHCYL1 Is a Novel Biomarker for Predicting Prognosis and Immunotherapy Response in Colorectal Cancer.Journal of oncology · 2022Article
- Blood-based DNA Methylation Biomarkers for Early Detection of Colorectal Cancer.Journal of proteomics & bioinformatics · 2018Article
- Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Article
- The prognostic yield of biomarkers harvested in chemotherapy-naive stage II colon cancer: can we separate the wheat from the chaff?Molecular medicine (Cambridge, Mass.) · 2016Article
- Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis.Journal of translational medicine · 2016Article
- The Prognostic Value of Microsatellite Instability,Molecular medicine (Cambridge, Mass.) · 2016Article
- An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients.Medicine · 2016Observational
- Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse.International journal of molecular sciences · 2016Article
- Mutanome and expression of immune response genes in microsatellite stable colon cancer.Oncotarget · 2016Article
- SNPase-ARMS qPCR: Ultrasensitive Mutation-Based Detection of Cell-Free Tumor DNA in Melanoma Patients.PloS one · 2015Article
- Systematic Analysis of Spleen Tyrosine Kinase Expression and its Clinical Outcomes in Various Cancers.Saudi journal of medicine & medical sciencesArticle
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer.
methodsWe sought to investigate various molecular subtypes defined by instability at microsatellites (MSI), changes in methylation patterns (CpG island methylator phenotype, CIMP) or copy number variation (CNV) in 8 genes. Stage II-III colon cancers (n = 64) were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA). Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression.
resultsThe CIMP phenotype occurred in 34% (22/64) and MSI in 27% (16/60) of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR) for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026). Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001), IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007), CDKN2A (p16) (OR of 2.0, 95% CI 1.1-3.6; P = 0.024), and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002) were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8) compared to survivors (CNV in 3 of 8). Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence.
conclusionsA high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.
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