Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups

被引：60

作者：

Thomas, Christian ^{[1
]}

Sill, Martin ^{[2
]}

Ruland, Vincent ^{[1
]}

Witten, Anika ^{[3
]}

Hartung, Stefan ^{[4
]}

Kordes, Uwe ^{[4
]}

Jeibmann, Astrid ^{[1
]}

Beschorner, Rudi ^{[5
]}

Keyvani, Kathy ^{[6
]}

Bergmann, Markus ^{[7
]}

Mittelbronn, Michel ^{[8
]}

Pietsch, Torsten ^{[9
]}

Felsberg, Joerg ^{[10
]}

Monoranu, Camelia M. ^{[11
,12
]}

Varlet, Pascale ^{[13
]}

Hauser, Peter ^{[14
]}

Olar, Adriana ^{[15
]}

Grundy, Richard G. ^{[16
]}

Wolff, Johannes E. ^{[17
]}

Korshunov, Andrey ^{[18
,19
,20
]}

Jones, David T. ^{[20
,21
,22
]}

Bewerunge-Hudler, Melanie ^{[23
]}

Hovestadt, Volker ^{[24
]}

von Deimling, Andreas ^{[18
,19
,20
]}

Pfister, Stefan M. ^{[20
,21
,22
]}

Paulus, Werner ^{[1
]}

Capper, David ^{[18
,19
,20
]}

Hasselblatt, Martin ^{[1
]}

机构：

[1] Univ Hosp Munster, Inst Neuropathol, Pottkamp 2, D-48149 Munster, Germany

[2] German Canc Res Ctr, Div Biostat, Heidelberg, Germany

[3] Med Fac Munster, Core Facil Genom, Munster, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany

[5] Univ Tubingen, Inst Pathol & Neuropathol, Dept Neuropathol, Tubingen, Germany

[6] Univ Duisburg Essen, Inst Neuropathol, Fac Med, Essen, Germany

[7] Klinikum Bremen Mitte, Dept Neuropathol, Bremen, Germany

[8] Goethe Univ Frankfurt, Edinger Inst, Inst Neurol, Frankfurt, Germany

[9] Univ Bonn, Med Ctr, Inst Neuropathol, Bonn, Germany

[10] Univ Dusseldorf, Dept Neuropathol, Dusseldorf, Germany

[11] Univ Wurzburg, Inst Pathol, Dept Neuropathol, Josef Schneider Str 2, Wurzburg, Germany

[12] CCCM, Wurzburg, Germany

[13] St Anna Hosp, Dept Neuropathol, Paris, France

[14] Semmelweis Univ, Dept Paediat 2, H-1085 Budapest, Hungary

[15] Univ Texas MD Anderson Canc Ctr, Mol Diagnost Lab, Dept Hematopathol, Houston, TX 77030 USA

[16] Univ Nottingham, Queens Med Ctr, Sch Med, Childrens Brain Tumour Res Ctr, Nottingham NG7 2RD, England

[17] Childrens Hosp, Dept Pediat Hematol Oncol & Blood & Marrow Transp, Cleveland Clin, Cleveland, OH USA

[18] Univ Heidelberg Hosp, Dept Neuropathol, Heidelberg, Germany

[19] German Res Ctr DKFZ, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[20] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[21] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[22] Univ Heidelberg Hosp, Dept Pediat Oncol & Hematol, D-69120 Heidelberg, Germany

[23] German Canc Res Ctr, Genom & Prote Core Facil, Microarray Unit, Heidelberg, Germany

[24] German Canc Res Ctr, Div Mol Genet, Heidelberg, Germany

来源：

NEURO-ONCOLOGY | 2016年 / 18卷 / 06期

关键词：

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

D O I：

10.1093/neuonc/nov322

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：790 / 796

页数：7

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