Biallelic FANCD1/BRCA2 mutations predisposing to glioblastoma multiforme with multiple oncogenic amplifications

Abstract

Fanconi anaemia (FA) caused by biallelic mutation in FANCD1/BRCA2 is rare but carries a high risk of early onset cancer. Medulloblastoma is well described in this cohort but reports of other brain tumours are uncommon. The molecular profile of tumours from FA patients is not well reported. A glioblastoma multiforme (GBM) from a 3-year-old patient with FA and confirmed biallelic BRCA2 mutations was submitted for methylation analysis. This revealed strong clustering with the K27 mutation subgroup and copy number analysis showed gains of chromosomes 1q, 4q, part of 7q, part of 8q and 17q with resultant amplifications of MDM4, CDK6, MET, MYC and PPM1D (WIP1). We also describe for the first time ..