Background: High-grade gliomas (HGG) occur in any central nervous system (CNS) location and any age. HGGs in teenagers/young adults (TYA) are understudied. This project aimed to characterise these tumours to support accurate patient stratification.
View Article and Find Full Text PDFCancer predisposition syndromes mediated by recessive cancer genes generate tumors via somatic variants (second hits) in the unaffected allele. Second hits may or may not be sufficient for neoplastic transformation. Here we performed whole-genome and whole-exome sequencing on 479 tissue biopsies from a child with neurofibromatosis type 1, a multisystem cancer-predisposing syndrome mediated by constitutive monoallelic NF1 inactivation.
View Article and Find Full Text PDFPilocytic astrocytoma (PA) is the commonest low-grade tumour affecting children and is frequently experienced as a chronic disease associated with extended treatment, periods of regrowth, and long-term disability. This contrasts with the view of PA as a benign tumour with positive clinical outcomes and raises the fundamental question of biologically driven change over time within these tumours, which will impact diagnosis, stratification, and management. To investigate the molecular, cellular, and pathological stability of PA we performed RNA sequencing, methylation array profiling, immunohistochemistry, and targeted panel DNA sequencing on a cohort of 15 PA patients with matched primary/longitudinal samples at a mean sampling interval of 2.
View Article and Find Full Text PDFFewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.
View Article and Find Full Text PDFBackground: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.
Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).