Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Schwalbe, E.; Hicks, D.; Rafiee, G.; Bashton, M.; Gohlke, H.; Enshaei, A.; Potluri, S.; Matthiesen, J.; Mather, M.; Taleongpong, P.; Chaston, R.; Silmon, A.; Curtis, A.; Lindsey, J.; Crosier, S.; Smith, A.; Goschzik, T.; Doz, F.; Rutkowski, S.; Lannering, B.; Pietsch, T.; Bailey, S.; Williamson, D.; Clifford, S.
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-13644-1
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation ofmi nimalm ethylati onc lassifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.