Christian Thomas1, Martin Sill1, Vincent Ruland1, Anika Witten1, Stefan Hartung1, Uwe Kordes1, Astrid Jeibmann1, Rudi Beschorner1, Kathy Keyvani1, Markus Bergmann1, Michel Mittelbronn1, Torsten Pietsch1, Jörg Felsberg1, Camelia M Monoranu1, Pascale Varlet1, Peter Hauser1, Adriana Olar1, Richard G Grundy1, Johannes E Wolff1, Andrey Korshunov1, David T Jones1, Melanie Bewerunge-Hudler1, Volker Hovestadt1, Andreas von Deimling1, Stefan M Pfister1, Werner Paulus1, David Capper1, Martin Hasselblatt1. 1. Institute of Neuropathology, University Hospital Münster, Münster, Germany (C.T., V.R., A.J., W.P., M.H.); Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany (M.S.); Core Facility Genomics of the Medical Faculty Münster, Münster, Germany (A.W.); Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.H., U.K.); Department of Neuropathology, Institute for Pathology and Neuropathology, University of Tübingen, Tübingen, Germany (R.B.); Faculty of Medicine, Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany (K.K.); Department of Neuropathology, Klinikum Bremen-Mitte, Bremen, Germany (M.B.); Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany (M.M.); Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany (T.P.); Department of Neuropathology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany (J.F.); Department of Neuropathology, Institute of Pathology, University of Würzburg, and Comprehensive Cancer Center Mainfranken (CCCM), Würzburg, Germany (C.M.M.); Department of Neuropathology, Sainte-Anne Hospital, Paris, France (P.V.); 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary (P.H.); Department of Hematopathology, Molecular Diagnostic Laboratory, The University of Texas MD Anderson Cancer Center, Houston, Texas (A.O.); Children's Brain Tumour Research Centre, School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK (R.G.G.); Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children's Hospital, Cleveland, Ohio (J.E.W.); Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany (A.K., A.v.D., D.C.); Clinical Cooperation Unit Neuropathology, German Research Center (DKFZ), Heidelberg, Germany (A.K., A.v.D., D.C.); German Cancer Consortium (DKTK), German Cancer Research Ce
Abstract
BACKGROUND: Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. METHODS: Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. RESULTS: Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. CONCLUSIONS: Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND:Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. METHODS: Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. RESULTS: Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. CONCLUSIONS: Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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