Medulloblastoma subgroups remain stable across primary and metastatic compartments
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- 作者：Xin Wang (1) (2)
Adrian M. Dubuc (1) (2)
Vijay Ramaswamy (1) (2) (3)
Stephen Mack (1) (2)
Deena M. A. Gendoo (4)
Marc Remke (1) (2)
Xiaochong Wu (1)
Livia Garzia (1)
Betty Luu (1)
Florence Cavalli (1)
John Peacock (1) (2)
Borja L贸pez (1)
Patryk Skowron (1) (2)
David Zagzag (5)
David Lyden (6)
Caitlin Hoffman (1) (7)
Yoon-Jae Cho (8)
Charles Eberhart (9)
Tobey MacDonald (10)
Xiao-Nan Li (11)
Timothy Van Meter (12)
Paul A. Northcott (13)
Benjamin Haibe-Kains (14) (4)
Cynthia Hawkins (15)
James T. Rutka (7)
Eric Bouffet (3)
Stefan M. Pfister (13)
Andrey Korshunov (16)
Michael D. Taylor (1) (7)
1. Developmental and Stem Cell Biology Program ; The Hospital for Sick Children ; University of Toronto ; Toronto ; ON ; Canada
2. Department of Laboratory Medicine and Pathobiology ; University of Toronto ; Toronto ; ON ; Canada
3. Division of Haematology/Oncology ; Hospital for Sick Children ; Toronto ; ON ; Canada
4. Bioinformatics and Computational Genomics Laboratory ; Princess Margaret Cancer Centre ; University Health Network ; Toronto ; ON ; Canada
5. Departments of Pathology and Neurosurgery ; NYU Langone Medical Center ; New York ; NY ; USA
6. Departments of Pediatrics ; Cell and Developmental Biology ; Weill Medical College of Cornell University ; New York ; NY ; USA
7. Division of Neurosurgery ; Hospital for Sick Children ; 555 University Ave ; Ste 1503 ; Toronto ; ON ; M5C 1X8 ; Canada
8. Department of Neurology and Neurological Sciences ; Stanford University School of Medicine ; Stanford ; CA ; USA
9. Departments of Pathology ; Ophthalmology and Oncology ; John Hopkins University School of Medicine ; Baltimore ; MD ; USA
10. Pediatric Neuro-Oncology Program ; Emory University School of Medicine ; Atlanta ; GA ; USA
11. Department of Pediatrics ; Brain Tumor Program ; Children鈥檚 Cancer Center ; Baylor College of Medicine ; Houston ; TX ; USA
12. Department of Pediatrics ; Virginia Commonwealth University School of Medicine ; Richmond ; VA ; USA
13. Division of Pediatric Neurooncology ; Department of Pediatric Hematology and Oncology ; German Cancer Consortium (DKTK) ; German Cancer Research Center (DKFZ) ; Heidelberg University Hospital ; Heidelberg ; Germany
14. Department of Medical Biophysics ; University of Toronto ; Toronto ; ON ; Canada
15. Department of Pathology ; Hospital for Sick Children ; Toronto ; ON ; Canada
16. Clinical Cooperation Unit Neuropathology ; German Cancer Research Center (DKFZ) ; Heidelberg ; Germany - 关键词：Medulloblastoma ; Metastasis ; Molecular subgroups ; Integrative genomics ; Gene expression ; DNA methylation
- 刊名：Acta Neuropathologica
- 出版年：2015
- 出版时间：March 2015
- 年：2015
- 卷：129
- 期：3
- 页码：449-457
- 全文大小：1,317 KB
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- 刊物主题：Medicine & Public Health
Pathology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0533
文摘
Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.