Document Detail


Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis.
MedLine Citation:
PMID:  22691720     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Childhood CNS primitive neuro-ectodermal brain tumours (PNETs) are very aggressive brain tumours for which the molecular features and best treatment approaches are unknown. We assessed a large cohort of these rare tumours to identify molecular markers to enhance clinical management of this disease.
METHODS: We obtained 142 primary hemispheric CNS PNET samples from 20 institutions in nine countries and examined transcriptional profiles for a subset of 51 samples and copy number profiles for a subset of 77 samples. We used clustering, gene, and pathway enrichment analyses to identify tumour subgroups and group-specific molecular markers, and applied immunohistochemical and gene-expression analyses to validate and assess the clinical significance of the subgroup markers.
FINDINGS: We identified three molecular subgroups of CNS PNETs that were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Patients with group 1 tumours were most often female (male:female ratio 0·61 for group 1 vs 1·25 for group 2 and 1·63 for group 3; p=0·043 [group 1 vs groups 2 and 3]), youngest (median age at diagnosis 2·9 years [95% CI 2·4-5·2] for group 1 vs 7·9 years [6·0-9·7] for group 2 and 5·9 years [4·9-7·8] for group 3; p=0·005), and had poorest survival (median survival 0·8 years [95% CI 0·5-1·2] in group 1, 1·8 years [1·4-2·3] in group 2 and 4·3 years [0·8-7·8] in group 3; p=0·019). Patients with group 3 tumours had the highest incidence of metastases at diagnosis (no distant metastasis:metastasis ratio 0·90 for group 3 vs 2·80 for group 1 and 5·67 for group 2; p=0·037).
INTERPRETATION: LIN28 and OLIG2 are promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.
FUNDING: Canadian Institute of Health Research, Brainchild/SickKids Foundation, and the Samantha Dickson Brain Tumour Trust.
Authors:
Daniel Picard; Suzanne Miller; Cynthia E Hawkins; Eric Bouffet; Hazel A Rogers; Tiffany S Y Chan; Seung-Ki Kim; Young-Shin Ra; Jason Fangusaro; Andrey Korshunov; Helen Toledano; Hideo Nakamura; James T Hayden; Jennifer Chan; Lucie Lafay-Cousin; Pingzhao Hu; Xing Fan; Karin M Muraszko; Scott L Pomeroy; Ching C Lau; Ho-Keung Ng; Chris Jones; Timothy Van Meter; Steven C Clifford; Charles Eberhart; Amar Gajjar; Stefan M Pfister; Richard G Grundy; Annie Huang
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2012-06-11
Journal Detail:
Title:  The lancet oncology     Volume:  13     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-31     Completed Date:  2012-10-11     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  838-48     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Division of Hematology-Oncology, Arthur and Sonia Labatt Brain Tumour Research Centre, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Basic Helix-Loop-Helix Transcription Factors / genetics*
Brain Neoplasms / genetics*,  mortality,  pathology
Cell Lineage / genetics
Chi-Square Distribution
Child
Child, Preschool
Cluster Analysis
Europe
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genomics* / methods
Humans
Immunohistochemistry
Japan
Kaplan-Meier Estimate
Male
Nerve Tissue Proteins / genetics*
Neuroectodermal Tumors, Primitive / genetics*,  mortality,  secondary
North America
Principal Component Analysis
Prognosis
RNA-Binding Proteins / genetics*
Reproducibility of Results
Republic of Korea
Retrospective Studies
Risk Assessment
Risk Factors
Tumor Markers, Biological / genetics*
Grant Support
ID/Acronym/Agency:
102684//Canadian Institutes of Health Research; P30 CA021765/CA/NCI NIH HHS; P30 HD018655/HD/NICHD NIH HHS; R01 CA109467/CA/NCI NIH HHS; R01 CA148621/CA/NCI NIH HHS; R01 CA163737/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/LIN-28 protein, human; 0/Nerve Tissue Proteins; 0/OLIG2 protein, human; 0/RNA-Binding Proteins; 0/Tumor Markers, Biological
Comments/Corrections
Comment In:
Lancet Oncol. 2012 Aug;13(8):753-4   [PMID:  22691719 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides analogues as potent HIV-1 non-...
Next Document:  Management of recurrent mechanical prosthetic tricuspid valve thrombosis in the perioperative period...