Epigenetic profiling reveals a subset of pediatric-type glioneuronal tumors characterized by oncogenic gene fusions involving several targetable kinases
Abstrakt
lioneuronal tumors (GNTs) are a diverse group of central nervous system (CNS) neoplasms that primarily affects children and young adults. Their histopathological diagnosis can be extremely challenging due to overlapping morphological features among the different (sub-)types.
In recent years, the use of next-generation sequencing and DNA methylation arrays revealed a large spectrum of different types of GNTs that are often characterized by a unique (epi-)genetic profile. However, the molecular landscape of GNT is far from being exhaustively described.
Interestingly, the vast majority of GNTs are driven by one of a variety of aberrations in the mitogen-activated protein kinase (MAPK) signaling pathway, including mutations, fusions or structural rearrangements in BRAF, NF1, FGFR1 or NTRK1/2/3, and other rarer alterations. Aberrant activation of the MAPK pathway is not only important from a diagnostic perspective, it also offers therapeutic opportunities since inhibitors are frequently available.