title: Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.
abstract: BACKGROUND
  Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination.
  
  
  METHODS
  MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors.
  
  
  RESULTS
  Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88).
  
  
  CONCLUSIONS
  The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups.
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Blüml
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Margol
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Rebekah J
authors.initials: RJ
authors.lastname: Kennedy
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Robison
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Marzieh
authors.initials: M
authors.lastname: Vali
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Long T
authors.initials: LT
authors.lastname: Hung
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Sakunthala
authors.initials: S
authors.lastname: Muthugounder
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Finlay
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Anat
authors.initials: A
authors.lastname: Erdreich-Epstein
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Floyd H
authors.initials: FH
authors.lastname: Gilles
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krieger
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Girish
authors.initials: G
authors.lastname: Dhall
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Marvin D
authors.initials: MD
authors.lastname: Nelson
authors.affiliation: Children's Hospital Los Angeles and The Saban Research Institute, Los Angeles, California (S.B., A.S.M., R.S., R.J.K., N.J.R., M.V., L.T.H., S.M., A.E-E., F.H.G., A.R.J., M.D.K., G.D., M.D.N., S.A.); Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California (S.B., M.D.N.); Rudi Schulte Research Institute, Santa Barbara, California (S.B., M.D.N.); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (R.S.); Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio (J.L.F.); Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California (A.E-E., F.H.G., A.R.J., S.A.); Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California (M.D.K.); Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California (A.S.M., N.J.R., A.E-E., G.D., S.A.).
authors.forename: Shahab
authors.initials: S
authors.lastname: Asgharzadeh
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008527:Medulloblastoma / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: MR spectroscopy; medulloblastoma; molecular subtypes