Zusammenfassung
Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic disease with substantial morbidities. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.
- 1,
- 6;
- 9;
- animals;
- astrocytoma,
- b-raf,
- base
- brain
- breakpoints;
- cell
- chemistry/genetics;
- chromosome
- chromosomes,
- conformation;
- factor,
- factors,
- fibroblast
- fusion,
- genetics/metabolism
- genetics/metabolism;
- growth
- human,
- humans;
- kinase
- line;
- map
- metabolism;
- mice;
- models,
- molecular;
- mutation;
- neoplasms,
- neoplastic,
- oncogene
- pair
- protein
- proteins
- proteins,
- proto-oncogene
- receptor,
- sequence;
- signaling
- system;
- transformation,
- trkb,
- type
Nutzer