Where can DNA (deoxyribonucleic acid) methylation testing be performed locally and internationally?

DNA Methylation Testing Locations Locally and Internationally

DNA methylation testing is best performed at academic tertiary centers with specialized expertise, particularly for specific conditions like medulloblastoma, where genome-wide DNA methylation with brain tumor classifier application is considered the gold standard for diagnosis and subgroup classification. 1

Academic and Clinical Testing Centers

• DNA methylation testing is available at academic centers in the United States and is widely performed in several European countries including France, Germany, and the United Kingdom 1
• For medulloblastoma and other central nervous system tumors, specialized testing should be referred to academic tertiary centers with expertise in this area 1
• The National Cancer Institute (NCI) and similar institutions perform integrated analysis incorporating histology, next-generation sequencing, and DNA methylation for CNS tumors 1

Testing Methods and Considerations

• Several analysis packages are available for studying DNA methylation differences, including methylkit and DSS (Dispersion Shrinkage for Sequencing) 1
• Testing methods include:
  • Bisulfite conversion-based methods (most popular approach) 2
  • Restriction enzyme-based approaches 2
  • Affinity enrichment-based assays using proteins with methylation binding domains or antibodies 2
• High-throughput methods include microarray hybridization technology and next-generation sequencing platforms that allow genomic mapping at single-nucleotide resolution 3, 4

International Availability

• DNA methylation testing is routinely performed in European countries (France, Germany, UK) as part of clinical protocols 1
• The European Organisation for Research and Treatment of Cancer (EORTC) incorporates DNA methylation testing as part of central neuropathology review in clinical trials 1
• Specialized testing centers exist internationally for genome-wide DNA methylation analysis in individuals with neurodevelopmental presentations and congenital anomalies 5

Clinical Applications

• DNA methylation testing has diagnostic utility in:
  • Cancer diagnosis and subtyping (particularly brain tumors) 1
  • Epigenetic aging clock measurements 1
  • Neurodevelopmental disorders and congenital anomalies 5
  • Obesity and smoking biomarkers 6

Quality Considerations When Selecting a Testing Center

• Look for centers that implement proper quality control measures including:
  • Filtering based on coverage levels and DNA methylation percentage 1
  • Correction for SNP genotypes when calling methylation 1
  • Appropriate statistical analysis methods for differential methylation 1
• Centers should have expertise in both the technical aspects of methylation testing and clinical interpretation of results 1

Pitfalls and Caveats

• DNA methylation testing results can be affected by:
  • PCR bias requiring filtering of bases with very high read coverage 1
  • Low read coverage (<10×) affecting statistical power 1
  • SNPs at CpG sites causing underestimation of DNA methylation levels 1
  • Overdispersion in statistical models requiring correction 1
• Different algorithms for detecting differentially methylated regions (DMRs) can lead to different DNA methylation values even when using the same whole-genome bisulfite sequencing data 1
• Interpretation of results requires specialized expertise, particularly for clinical applications 1

When seeking DNA methylation testing, it's crucial to select centers with appropriate expertise in both the technical aspects of the testing and clinical interpretation of the results to ensure accurate diagnosis and treatment decisions.