TMOD-05. C-MYC OVEREXPRESSION INDUCES CHOROID PLEXUS PAPILLOMAS THROUGH A T-CELL MEDIATED INFLAMMATORY MECHANISM

Abstract

Choroid plexus tumours (CPTs) account for up to 20% of brain tumours in children under 2 years of age. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only few high fidelity mouse models of p53-deficient malignant CPTs are available. We show here that c-Myc overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. Together with the deregulation of the IL36/IL1RL2 axis observed in c-Myc-dependent murine and c-MYC positive human CPTs, our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs rather than surgical therapy.