116. Integrating methylation profiling into adult brain tumor diagnostics - the Australian experience

Abstract

While genomic data has revolutionized brain tumor diagnostics in the past decade, methylation profiling has emerged as a valuable classification tool. Methylation profiling is increasingly being shown to be a compelling diagnostic adjunct in pediatric brain tumors. We therefore sought to delineate its most useful indications in diagnostically challenging adult tumors, in combination with current genomic classification parameters. Here we detail our initial experience at a national tertiary referral centre for neuro-oncology diagnostics in Australia. To date, we have profiled 80 such cases using Illumina MethylationEPIC arrays, with DNA extracted from formalin fixed paraffin embedded tissue. Methylation data was analysed using the German Cancer Research Centre (DKFZ) Brain Tumor Methylation Classifier (v12.3). 50 tumours had undergone a concomitant next generation sequencing (NGS) targeted glioma gene panel (20 low grade gliomas/glioneuronal tumors; 30 high grade gliomas). Concordance between the histological diagnosis and methylation class result (with recommended calibrated score ?0.84) was observed in 75% of classifiable cases. Of the low grade gliomas (LGGs), 45% of diagnoses were unresolved by NGS. Of these unresolved cases, the diagnosis of 1 case was resolved by methylation profiling (11%). Of the high grade gliomas (HGGs), 57% of diagnoses were unresolved by NGS. By contrast, 65% of unresolved HGG cases were resolved by methylation profiling, largely comprising ependymomas, medulloblastomas and high grade neuroepithelial tumours. Our preliminary results indicate that methylation profiling has an important role in diagnostically challenging, high grade adult brain tumors, particularly where the tumor entity is also found in the pediatric population.