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Neuro Oncol. 2016 Jun;18(6):790-6. doi: 10.1093/neuonc/nov322. Epub 2016 Jan 28.

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

Author information

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.

KEYWORDS:

atypical choroid plexus papilloma; choroid plexus carcinoma; copy-number alterations; epigenetics; prognosis

PMID:
26826203
PMCID:
PMC4864264
DOI:
10.1093/neuonc/nov322
[Indexed for MEDLINE]
Free PMC Article

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