Stefan Blüml1, Ashley S Margol1, Richard Sposto1, Rebekah J Kennedy1, Nathan J Robison1, Marzieh Vali1, Long T Hung1, Sakunthala Muthugounder1, Jonathan L Finlay1, Anat Erdreich-Epstein1, Floyd H Gilles1, Alexander R Judkins1, Mark D Krieger1, Girish Dhall1, Marvin D Nelson1, Shahab Asgharzadeh1. 1. 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.).
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.
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: Arzu Kovanlikaya; Ashok Panigrahy; Mark D Krieger; Ignacio Gonzalez-Gomez; Nilesh Ghugre; J Gordon McComb; Floyd H Gilles; Marvin D Nelson; Stefan Blüml Journal: Radiology Date: 2005-09 Impact factor: 11.105
Authors: Roger J Packer; Amar Gajjar; Gilbert Vezina; Lucy Rorke-Adams; Peter C Burger; Patricia L Robertson; Lisa Bayer; Deborah LaFond; Bernadine R Donahue; MaryAnne H Marymont; Karin Muraszko; James Langston; Richard Sposto Journal: J Clin Oncol Date: 2006-09-01 Impact factor: 44.544
Authors: Amar Gajjar; Murali Chintagumpala; David Ashley; Stewart Kellie; Larry E Kun; Thomas E Merchant; Shaio Woo; Greg Wheeler; Valerie Ahern; Matthew J Krasin; Maryam Fouladi; Alberto Broniscer; Robert Krance; Gregory A Hale; Clinton F Stewart; Robert Dauser; Robert A Sanford; Christine Fuller; Ching Lau; James M Boyett; Dana Wallace; Richard J Gilbertson Journal: Lancet Oncol Date: 2006-10 Impact factor: 41.316
Authors: Ashley S Margol; Nathan J Robison; Janahan Gnanachandran; Long T Hung; Rebekah J Kennedy; Marzieh Vali; Girish Dhall; Jonathan L Finlay; Anat Erdreich-Epstein; Mark D Krieger; Rachid Drissi; Maryam Fouladi; Floyd H Gilles; Alexander R Judkins; Richard Sposto; Shahab Asgharzadeh Journal: Clin Cancer Res Date: 2014-10-24 Impact factor: 12.531
Authors: Margaret C Thompson; Christine Fuller; Twala L Hogg; James Dalton; David Finkelstein; Ching C Lau; Murali Chintagumpala; Adekunle Adesina; David M Ashley; Stewart J Kellie; Michael D Taylor; Tom Curran; Amar Gajjar; Richard J Gilbertson Journal: J Clin Oncol Date: 2006-03-27 Impact factor: 44.544
Authors: Edward C Schwalbe; Daniel Williamson; Janet C Lindsey; Dolores Hamilton; Sarra L Ryan; Hisham Megahed; Miklós Garami; Peter Hauser; Bożena Dembowska-Baginska; Danuta Perek; Paul A Northcott; Michael D Taylor; Roger E Taylor; David W Ellison; Simon Bailey; Steven C Clifford Journal: Acta Neuropathol Date: 2013-01-05 Impact factor: 17.088
Authors: A Panigrahy; M D Krieger; I Gonzalez-Gomez; X Liu; J G McComb; J L Finlay; M D Nelson; F H Gilles; S Blüml Journal: AJNR Am J Neuroradiol Date: 2006-03 Impact factor: 3.825
Authors: James B McAlpine; Shao-Nong Chen; Andrei Kutateladze; John B MacMillan; Giovanni Appendino; Andersson Barison; Mehdi A Beniddir; Maique W Biavatti; Stefan Bluml; Asmaa Boufridi; Mark S Butler; Robert J Capon; Young H Choi; David Coppage; Phillip Crews; Michael T Crimmins; Marie Csete; Pradeep Dewapriya; Joseph M Egan; Mary J Garson; Grégory Genta-Jouve; William H Gerwick; Harald Gross; Mary Kay Harper; Precilia Hermanto; James M Hook; Luke Hunter; Damien Jeannerat; Nai-Yun Ji; Tyler A Johnson; David G I Kingston; Hiroyuki Koshino; Hsiau-Wei Lee; Guy Lewin; Jie Li; Roger G Linington; Miaomiao Liu; Kerry L McPhail; Tadeusz F Molinski; Bradley S Moore; Joo-Won Nam; Ram P Neupane; Matthias Niemitz; Jean-Marc Nuzillard; Nicholas H Oberlies; Fernanda M M Ocampos; Guohui Pan; Ronald J Quinn; D Sai Reddy; Jean-Hugues Renault; José Rivera-Chávez; Wolfgang Robien; Carla M Saunders; Thomas J Schmidt; Christoph Seger; Ben Shen; Christoph Steinbeck; Hermann Stuppner; Sonja Sturm; Orazio Taglialatela-Scafati; Dean J Tantillo; Robert Verpoorte; Bin-Gui Wang; Craig M Williams; Philip G Williams; Julien Wist; Jian-Min Yue; Chen Zhang; Zhengren Xu; Charlotte Simmler; David C Lankin; Jonathan Bisson; Guido F Pauli Journal: Nat Prod Rep Date: 2018-07-13 Impact factor: 13.423
Authors: Pamela Franco; Irene Huebschle; Carl Philipp Simon-Gabriel; Karam Dacca; Oliver Schnell; Juergen Beck; Hansjoerg Mast; Horst Urbach; Urs Wuertemberger; Marco Prinz; Jonas A Hosp; Daniel Delev; Irina Mader; Dieter Henrik Heiland Journal: Cancers (Basel) Date: 2021-05-17 Impact factor: 6.639