title: Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype.
abstract: BACKGROUND
  Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity.
  
  
  METHODS
  We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain.
  
  
  RESULTS
  Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. "Not otherwise specified" (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs.
  
  
  CONCLUSIONS
  Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bergthold
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Pratiti
authors.initials: P
authors.lastname: Bandopadhayay
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Shakti
authors.initials: S
authors.lastname: Ramkissoon
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Lori
authors.initials: L
authors.lastname: Ramkissoon
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rich
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Cecile L
authors.initials: CL
authors.lastname: Maire
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Paolella
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schumacher
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Barbara
authors.initials: B
authors.lastname: Tabak
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Ruben
authors.initials: R
authors.lastname: Ferrer-Luna
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Memet
authors.initials: M
authors.lastname: Ozek
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Aydin
authors.initials: A
authors.lastname: Sav
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Sandro
authors.initials: S
authors.lastname: Santagata
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Patrick Yung
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Liliana C
authors.initials: LC
authors.lastname: Goumnerova
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Charles
authors.initials: C
authors.lastname: Stiles
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Rosalind
authors.initials: R
authors.lastname: Segal
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Todd
authors.initials: T
authors.lastname: Golub
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chan
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., C.S., R.S., R.B.); Broad Institute, Cambridge, Massachusetts (G.B., P.B., B.R.P., S.E.S., B.T., R.F.-L., T.G., R.B.); Pediatric Neuro-Oncology Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (P.B., L.C.G., M.W.K.); Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Y.H.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.R., S.S., P.Y.W., A.H.L., K.L.L., J.A.C.); Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.R., L.R., B.R., C.L.M., K.L.L.); Department of Neurosurgery, Acibadem University Medical Center, Istanbul, Turkey (M.O.); Department of Pathology, Acibadem University Medical Center, Istanbul, Turkey (A.S.); Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts (L.C.G.); Departement de Cancerologie de l'enfant et de l'adolescent, Gustave Roussy and Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique, Université Paris-Sud, Villejuif, France (J.G.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.).
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome
keywords: BRAF duplication; BRAF mutation; expression; heterogeneity; pediatric low-grade glioma
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