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

Aly Abdelkareem
Laveniya Satgunaseelan

Dr. Laveniya Satgunaseelan graduated MBBS(Hons), BMedSc(Hons) from Monash University, Melbourne, Australia, in 2007. She initially was an accredited neurosurgical resident, after which she made a career change to surgical pathology. Laveniya trained in surgical pathology at Royal Prince Alfred Hospital (RPAH) and Douglass Hanly Moir Pathology, both in Sydney, Australia. During this time, she underwent training in molecular pathology, melanoma pathology and neuropathology. After gaining Fellowship of the Royal College of Pathologists of Australasia (RCPA) in 2018, Laveniya spent a year working in general surgical pathology, with subspecialty practice in head and neck pathology, at RPAH, one of the largest tertiary cancer referral centers in Australia. She then moved to the molecular service at the Department of Neuropathology at RPAH, which caters to the east coast of Australia and New Zealand. Laveniya also serves on the Cancer Scientific Advisory Committee of the RCPA, whose aim is to ensure quality and precision in cancer services in Australasia. She is currently undertaking a PhD at the University of Sydney in the genomic landscape of tongue cancer in young female patients. She is also an active member of the ClinGen Somatic Cancer Working Group and its Pediatric Cancer Taskforce, and is the current co-chair of the Histone H3 Somatic Cancer Variant Curation Expert Panel (SC-VCEP). Laveniya is passionate about equity of access to cancer genomic services.


Laveniya Satgunaseelan, Maggie Lee, Grace Wei, Shalima Nair

Royal Prince Alfred Hospital, Sydney, NSW, Australia

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.