title: Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation.
abstract: Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De-identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana-Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease.
authors.affiliation: Children's Cancer Centre, Royal Children's Hospital, 50 Flemington Road, Parkville, Melbourne, VIC, 3052, Australia. ajdodgshun@gmail.com.|Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia. ajdodgshun@gmail.com.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dodgshun
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: SantaCruz
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Medical Oncology, Dana-Faber Cancer Institute, Boston, 02115, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.|Department of Pathology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Shakti H
authors.initials: SH
authors.lastname: Ramkissoon
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Hayley
authors.initials: H
authors.lastname: Malkin
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bergthold
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Manley
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Chi
authors.affiliation: Department of Pathology, Royal Children's Hospital, Melbourne, VIC, 3052, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.|Department of Neurosurgery, Boston Children's Hospital, Boston, MA, USA.|Department of Neurosurgery, Harvard Medical School, Boston, MA, USA.
authors.forename: Liliana
authors.initials: L
authors.lastname: Goumnerova
authors.affiliation: Children's Cancer Centre, Royal Children's Hospital, 50 Flemington Road, Parkville, Melbourne, VIC, 3052, Australia.|Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Sullivan
authors.affiliation: Department of Medical Oncology, Dana-Faber Cancer Institute, Boston, 02115, USA.|Broad Institute of MIT and Harvard, Cambridge, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.|Department of Pathology, Boston Children's Hospital, Boston, MA, USA.|Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Ligon
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Department of Medical Oncology, Dana-Faber Cancer Institute, Boston, 02115, USA.|Broad Institute of MIT and Harvard, Cambridge, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Herrington
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.affiliation: Children's Cancer Centre, Royal Children's Hospital, 50 Flemington Road, Parkville, Melbourne, VIC, 3052, Australia.|Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia.
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Hansford
authors.affiliation: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Longwood Ave, Boston, 02115, USA. Pratiti_Bandopadhayay@dfci.harvard.edu.|Harvard Medical School, Boston, MA, USA. Pratiti_Bandopadhayay@dfci.harvard.edu.|Broad Institute of MIT and Harvard, Cambridge, USA. Pratiti_Bandopadhayay@dfci.harvard.edu.|Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. Pratiti_Bandopadhayay@dfci.harvard.edu.
authors.forename: Pratiti
authors.initials: P
authors.lastname: Bandopadhayay
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D012189:Retrospective Studies; D013116:Spinal Cord; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf
keywords: Glioneuronal; Leptomeningeal neoplasms; Oligodendroglioma; Pediatric glioma; Proto-oncogene proteins B-raf