Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma
By David T. W. Jones, B. Hutter, N. Jäger, A. Korshunov, M. Kool, H. Warnatz, T. Zichner, S. Lambert, M. Ryzhova, Dong Anh Khuong Quang and 65 more. Nature Genetics, 2013
747 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Neurology
View Paper: https://www.semanticscholar.org/paper/8c799fa0fe3fb50c4a1ba581cf0e20058c379037
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
- H. Rupasinghe
- E. McGowan
- Naiara Orrego Lagarón
- Indu Parmar
- A. Jha
- Khushwant S. Bhullar
- Basil P. Hubbard
Citations in the corpus
- Impacts of Neanderthal-introgressed sequences on the landscape of human gene expression (2017, neutral): “…(Gray et al., 2007), autism (Correia et al., 2010), obsessive-compulsive disorder (Alonso et al., 2008), Alzheimer’s disease (Chen et al., 2008), anorexia nervosa (Ribases et al., 2005), nicotine dependence (Li et al., 2008; Beuten et al., 2007), and pilocytic astrocytoma (Jones et al., 2013).”
- Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma (2016, neutral): “Pilocytic astrocytomas are characterized by frequent alterations in the MAPK pathway, such as FGFR1 mutations, KIAA1549-BRAF and NTRK2 fusions (Jones et al., 2013).”
- Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “These include mutations in neurotrophic growth factor receptor which are involved in pilocytic astrocytoma, the most common childhood brain tumor [58].”