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Updated: Nov 18, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Genome-wide DNA methylation profiling is able to identify prefibrotic PMF cases at risk for progression to
Ulrich Lehmann1, Helge Stark2, Stephan Bartels2
1Institute of Pathology, Medical School Hannover, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. Lehmann.Ulrich@MH-Hannover.de.
Background:
Patients suffering from the BCR-ABL1-negative myeloproliferative disease prefibrotic primary myelofibrosis (pre-PMF) have a certain risk for progression to myelofibrosis. Accurate risk estimation for this fibrotic progression is of prognostic importance and clinically relevant. Commonly applied risk scores are based on clinical, cytogenetic, and genetic data but do not include epigenetic modifications. Therefore, we evaluated the assessment of genome-wide DNA methylation patterns for their ability to predict fibrotic progression in PMF patients.
Results:
For this purpose, the DNA methylation profile was analyzed genome-wide in a training set of 22 bone marrow trephines from patients with either fibrotic progression (n = 12) or stable disease over several years (n = 10) using the 850 k EPIC array from Illumina. The DNA methylation classifier constructed from this data set was validated in an independently measured test set of additional 11 bone marrow trephines (7 with stable disease, 4 with fibrotic progress). Hierarchical clustering of methylation β-values and linear discriminant classification yielded very good discrimination between both patient groups. By gene ontology analysis, the most differentially methylated CpG sites are primarily associated with genes involved in cell-cell and cell-matrix interactions.
Conclusions:
In conclusion, we could show that genome-wide DNA methylation profiling of bone marrow trephines is feasible under routine diagnostic conditions and, more importantly, is able to predict fibrotic progression in pre-fibrotic primary myelofibrosis with high accuracy.
Insights
Genome-wide DNA methylation profiling accurately predicts fibrotic progression in prefibrotic primary myelofibrosis (pre-PMF). This epigenetic assessment offers a novel prognostic tool for patients with this BCR-ABL1-negative myeloproliferative neoplasm.
Area of Science:
- Epigenetics
- Hematology
- Oncology
Background:
- Prefibrotic primary myelofibrosis (pre-PMF) carries a risk of progression to myelofibrosis.
- Current risk scores lack epigenetic data, limiting prognostic accuracy.
- Epigenetic modifications may offer new insights into disease progression.
Purpose of the Study:
- To evaluate genome-wide DNA methylation patterns for predicting fibrotic progression in pre-PMF.
- To assess the clinical relevance of epigenetic modifications in myeloproliferative neoplasms.
- To develop a novel classifier for fibrotic progression risk.
Main Methods:
- Genome-wide DNA methylation analysis using the 850k EPIC array on bone marrow trephines.
- Training set (n=22) and validation set (n=11) of pre-PMF patients.
- Hierarchical clustering and linear discriminant classification for predictive modeling.
Main Results:
- A DNA methylation classifier demonstrated high accuracy in predicting fibrotic progression.
- Differential methylation analysis identified genes involved in cell-cell and cell-matrix interactions.
- The method proved feasible under routine diagnostic conditions.
Conclusions:
- Genome-wide DNA methylation profiling is a viable tool for predicting fibrotic progression in pre-PMF.
- This epigenetic approach enhances prognostic accuracy beyond traditional risk scores.
- The findings support the integration of DNA methylation analysis in managing pre-PMF.
