Microarray-Based DNA Methylation Profiling: Validation Considerations for Clinical Testing

Abstract

Microarray-based methylation profiling has emerged as a valuable tool for refining diagnoses and revealing novel tumor subtypes, particularly in central nervous system tumors. Despite the increasing adoption of this technique in clinical genomic laboratories, no technical standards have been published in establishing minimum criteria for test validation. A working group with experience and expertise in DNA-based methylation profiling tests on CNS tumors collaborated to develop practical discussion points and focus on important considerations for validating this test in clinical laboratory settings. We summarize our experiences in validating this methodology in a clinical setting. Specifically, we highlight the advantages and challenges associated with utilizing an in-house classifier compared to a third-party classifier. Additionally, we share our experiences in demonstrating the assay's sensitivity and specificity, establishing minimum sample criteria, and implementing quality control metrics. As methylation profiling for tumor classification expands to other tumor types and continues to evolve for various other applications, the critical considerations described here are expected to serve as a guidance for future efforts in establishing professional guidelines for this assay.