P05.04.A Disconcordance between different molecular methods to assess homozygous deletion of theCDKN2A/B locus in IDH-mutant astrocytomas

Abstract Background The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS 5), includes molecular parameters for both diagnosis and grading in addition to histological features. For IDH-mutant astrocytoma, homozygous deletion (HD) of CDKN2A/B now results in WHO grade 4, even in the absence of microvascular proliferation or necrosis. CDKN2A/B deletions can be determined by various techniques including shallow and targeted sequencing, and using genome wide DNA-methylation arrays. Various algorithms to call deletions also exist for each platform. Concordance between the various techniques and algorithms is however unknown. Because of the importance to properly call CDKN2A/B deletions, we compared two techniques to call HD in IDH-mutant astrocytoma patients. Methods Samples from 110 IDH-mutant astrocytoma patients enrolled in the GLASS-NL study, and therefore samples from at least two surgical resections per patient, were available. Overall survival (OS) was measured from date of first surgery. Both DNA-methylation data and shallow whole-genome sequencing (sWGS) was collected from 219 samples from 101 patients. For DNA-methylation analysis, HD of CDKN2A/B was defined by