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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
DNA methylation-based age estimation in pediatric healthy tissues and brain tumors
Teresia Kling1, Anna Wenger1, Helena Carén1
1Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Dedicated DNA methylation clocks are crucial for accurately assessing pediatric age and understanding pediatric brain tumors. Clocks trained on children performed best, with specific clocks showing accuracy in different tissues and potential as prognostic biomarkers.
Area of Science:
- Epigenetics
- Developmental Biology
- Pediatric Oncology
Background:
- Existing DNA methylation clocks are primarily trained on adult samples, limiting their accuracy for children.
- Epigenetic alterations play a significant role in pediatric tumor development.
- Accurate methylation age estimation in children is needed for research and clinical applications.
Purpose of the Study:
- To evaluate the performance of seven DNA methylation clocks in various tissues from healthy children.
- To identify the optimal methylation clock for pediatric cohorts.
- To analyze DNA methylation age acceleration in pediatric brain tumors and its correlation with prognosis.
Main Methods:
- Tested seven DNA methylation clocks across multiple tissue types from healthy pediatric samples.
- Assessed clock accuracy by correlating methylation age with chronological age.
- Analyzed methylation age in pediatric brain tumor samples, stratifying by tumor subtype.
Main Results:
- Methylation clocks trained on pediatric samples demonstrated superior accuracy across all tested tissues.
- The Skin and Blood clock was most accurate for blood, PedBE for saliva/buccal samples, and Horvath for brain tissue.
- Horvath methylation age was accelerated in pediatric brain tumors, with subtype-specific patterns and correlations with prognosis.
Conclusions:
- Pediatric-specific DNA methylation clocks are essential for accurate age estimation in children.
- Methylation age acceleration in pediatric brain tumors shows potential as a prognostic biomarker.
- Further research is warranted to explore the clinical utility of methylation age in pediatric oncology.
Abstract:
Several DNA methylation clocks have been developed to reflect chronological age of human tissues, but most clocks have been trained on adult samples. The rapid methylome changes in children and the role of epigenetics in pediatric tumors calls for tools accurately estimating methylation age in children. We aimed to evaluate seven methylation clocks in multiple tissues from healthy children to inform future studies on the optimal clock for pediatric cohorts, and analyzed the methylation age in brain tumors. We found that clocks trained on pediatric samples were the best in all tested tissues, highlighting the need for dedicated clocks. For blood samples, the Skin and blood clock had the best correlation with chronological age, while PedBE was the most accurate for saliva and buccal samples, and Horvath for brain tissue. Horvath methylation age was accelerated in pediatric brain tumors and the acceleration was subtype-specific for atypical teratoid rhabdoid tumor (ATRT), ependymoma, medulloblastoma and glioma. The subtypes with the highest acceleration corresponded to the worst prognostic categories in ATRT, ependymoma and glioma, whereas the relationship was reversed in medulloblastoma. This suggests that methylation age has potential as a prognostic biomarker in pediatric brain tumors and should be further explored.
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