Related Experiment Video
Updated: Jun 29, 2025
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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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Hypermethylated Colorectal Cancer Tumours Present a Myc-Driven Hypermetabolism with a One-Carbon Signature Associated
Christophe Desterke1, Fanny Jaulin2, Emmanuel Dornier2,3
1Inserm U1310, Faculté de Médecine, Université Paris Saclay, F-94800 Villejuif, France.
Biomedicines
|March 28, 2024
Summary
Colorectal cancer (CRC) with high CpG-island methylation (CIMP) shows increased metabolism, particularly in carbohydrate and folate pathways. This metabolic rewiring, linked to the Myc oncogene, can predict immunotherapy response and patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death.
- The CpG-island methylation pathway (CIMP) is linked to poor prognosis, chemoresistance, and specific oncogene mutations (KRAS/BRAF).
- Metabolic alterations in CIMP-high CRC remain largely unexplored.
Purpose of the Study:
- To investigate metabolic dysregulations associated with tumor methylation in colorectal cancer.
- To explore the role of oncogenes like Myc in CIMP-driven metabolic reprogramming.
- To identify transcriptomic biomarkers for predicting treatment response and prognosis in CRC.
Main Methods:
- Transcriptome analysis of colorectal cancer tumors.
- Evaluation of metabolic pathway activation in CIMP-high versus CIMP-low tumors.
- Identification of epigenetic targets and gene signatures associated with methylation levels.
Main Results:
- CIMP-high CRC tumors exhibit hypermetabolism, activating carbohydrate, folate, sphingolipid, and arachidonic acid pathways.
- A significant portion of these genes are Myc targets, influencing carboxylic acid, tetrahydrofolate, nucleobase, and oxoacid metabolism.
- Expression of GAPDH, TYMS, DHFR, and TK1 predicts methylation status, microsatellite instability (MSI), and mismatch repair (MMR) deficiency, key immunotherapy response indicators.
- CIMP tumors show increased one-carbon metabolism, linked to worse prognosis and hypermethylation.
Conclusions:
- Metabolic reprogramming is a hallmark of CIMP-high colorectal cancer.
- Transcriptomic profiling, particularly Myc-related gene signatures, can identify biomarkers for predicting immunotherapy response and patient stratification.
- Targeting one-carbon metabolism may offer therapeutic strategies for CIMP-driven CRC.
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