Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma
Autor/innen
- D.T.W. Jones
- B. Hutter
- N. Jäger
- A. Korshunov
- M. Kool
- H.J. Warnatz
- T. Zichner
- S.R. Lambert
- M. Ryzhova
- D.A.K. Quang
- A.M. Fontebasso
- A.M. Stütz
- S. Hutter
- M. Zuckermann
- D. Sturm
- J. Gronych
- B. Lasitschka
- S. Schmidt
- H. Seker-Cin
- H. Witt
- M. Sultan
- M. Ralser
- P.A. Northcott
- V. Hovestadt
- S. Bender
- E. Pfaff
- S. Stark
- D. Faury
- J. Schwartzentruber
- J. Majewski
- U.D. Weber
- M. Zapatka
- B. Raeder
- M. Schlesner
- C.L. Worth
- C.C. Bartholomae
- C. von Kalle
- C.D. Imbusch
- S. Radomski
- C. Lawerenz
- P. van Sluis
- J. Koster
- R. Volckmann
- R. Versteeg
- H. Lehrach
- C. Monoranu
- B. Winkler
- A. Unterberg
- C. Herold-Mende
- T. Milde
- A.E. Kulozik
- M. Ebinger
- M.U. Schuhmann
- Y.J. Cho
- S.L. Pomeroy
- A. von Deimling
- O. Witt
- M.D. Taylor
- S. Wolf
- M.A. Karajannis
- C.G. Eberhart
- W. Scheurlen
- M. Hasselblatt
- K.L. Ligon
- M.W. Kieran
- J.O. Korbel
- M.L. Yaspo
- B. Brors
- J. Felsberg
- G. Reifenberger
- V.P. Collins
- N. Jabado
- R. Eils
- P. Lichter
- S.M. Pfister
Journal
- Nature Genetics
Quellenangabe
- Nat Genet 45 (8): 927-932
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.