CNS Embryonal Tumour With PLAG Family Gene Alteration: Failure of Response to RET Inhibition

A rare central nervous system (CNS) embryonal tumour characterised by alterations in the PLAG family gene has recently been reported. RET is a direct PLAGL1/2 target and RET inhibitors were thought to have therapeutic potential in this tumour. In a patient with a CNS tumour with PLAGL2 amplification, we show RET inhibition had no clinical effect. Transcriptomic profiling demonstrated low RET levels with associated low levels of RET phosphorylation (pRET). Measurement of RET/pRET activity may be useful in predicting response to RET inhibition in these tumours.