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Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis.
- Source :
-
The Lancet. Oncology [Lancet Oncol] 2012 Aug; Vol. 13 (8), pp. 838-48. Date of Electronic Publication: 2012 Jun 11. - Publication Year :
- 2012
-
Abstract
- 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.<br />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.<br />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).<br />Interpretation: LIN28 and OLIG2 are promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.<br />Funding: Canadian Institute of Health Research, Brainchild/SickKids Foundation, and the Samantha Dickson Brain Tumour Trust.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Brain Neoplasms mortality
Brain Neoplasms pathology
Cell Lineage genetics
Chi-Square Distribution
Child
Child, Preschool
Cluster Analysis
Europe
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Japan
Kaplan-Meier Estimate
Male
Neuroectodermal Tumors, Primitive mortality
Neuroectodermal Tumors, Primitive secondary
North America
Oligodendrocyte Transcription Factor 2
Principal Component Analysis
Prognosis
Reproducibility of Results
Republic of Korea
Retrospective Studies
Risk Assessment
Risk Factors
Basic Helix-Loop-Helix Transcription Factors genetics
Biomarkers, Tumor genetics
Brain Neoplasms genetics
Genomics methods
Nerve Tissue Proteins genetics
Neuroectodermal Tumors, Primitive genetics
RNA-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1474-5488
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Lancet. Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 22691720
- Full Text :
- https://doi.org/10.1016/S1470-2045(12)70257-7