title: No correlation between NF1 mutation position and risk of optic pathway glioma in 77 unrelated NF1 patients.
abstract: Neurofibromatosis type 1 (NF1) is a common monogenic disorder whereby affected individuals are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs, occurring in ~15 to 20 % of cases). So far, no definite genotype-phenotype correlation determining NF1 patients at risk for tumor formation has been described, although enrichment for mutations in the 5' region of the NF1 gene in OPG patients has been suggested. We used whole exome sequencing, targeted sequencing, and copy number analysis to screen 77 unrelated NF1 patients with (n = 41) or without (n = 36; age ≥10 years) optic pathway glioma for germline NF1 alterations. We identified germline NF1 mutations in 69 of 77 patients (90 %), but no genotype-phenotype correlation was observed. Our data using a larger patient cohort did not confirm the previously reported clustering of mutations in the 5' region of the NF1 gene in patients with OPG. Thus, NF1 mutation location should not currently be used as a clinical criterion to assess the risk of developing OPGs.
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hutter
authors.affiliation: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK) Core Center Heidelberg, Heidelberg, Germany.|Institute of Computer Science, Freie Universität Berlin, Berlin, Germany.|Institute of Medical Genetics and Human Genetics, Charité University Hospital, Berlin, Germany.
authors.forename: Rosario M
authors.initials: RM
authors.lastname: Piro
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Waszak
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Kehrer-Sawatzki
authors.affiliation: Department of Oral and Cranio-Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Friedrich
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lassaletta
authors.affiliation: German Cancer Consortium (DKTK) Core Center Heidelberg, Heidelberg, Germany.|Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.|National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Witt
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Research Unit, Heidelberg, Germany.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Korbel
authors.affiliation: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK) Core Center Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.affiliation: Department of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.|Centre for Neurofibromatosis, Centre for Rare Diseases Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK) Partner Site Tübingen, Tübingen, Germany.
authors.forename: Martin U
authors.initials: MU
authors.lastname: Schuhmann
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.|German Cancer Consortium (DKTK) Core Center Heidelberg, Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.|National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.affiliation: Department of Neurology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. v.mautner@uke.de.
authors.forename: Victor F
authors.initials: VF
authors.lastname: Mautner
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. davidjones@cantab.net.|German Cancer Consortium (DKTK) Core Center Heidelberg, Heidelberg, Germany. davidjones@cantab.net.
authors.forename: David T W
authors.initials: DTW
authors.lastname: Jones
mesh_terms: D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D059472:Exome / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics*; D020339:Optic Nerve Glioma / Q000209:etiology*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D025542:Neurofibromin 1