ArticleNeuro-oncology2008
Global analysis of the medulloblastoma epigenome identifies disease-subgroup-specific inactivation of COL1A2.
Article in Neuro-oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
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- The 2016 WHO Classification of Tumours of the Central Nervous System: The Major Points of Revision.Neurologia medico-chirurgica · 2017Review
- Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.Oncotarget · 2016Article
- Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance.Oncogene · 2015Article
- Identification of the collagen type 1 α 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma.BMC cancer · 2014Article
- Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN.Oncogenesis · 2013Article
- DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies.Acta neuropathologica · 2013Article
- Deregulated chromatin remodeling in the pathobiology of brain tumors.Neuromolecular medicine · 2013Review
- Genome-wide and species-wide in silico screening for intragenic MicroRNAs in human, mouse and chicken.PloS one · 2013Article
- Global gene expression profiling confirms the molecular fidelity of primary tumor-based orthotopic xenograft mouse models of medulloblastoma.Neuro-oncology · 2012Article
- Epigenetic regulation of S100 protein expression.Clinical epigenetics · 2011Article
- Rapid diagnosis of medulloblastoma molecular subgroups.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- Inhibition of tumor cell migration and invasion through knockdown of Rac1 expression in medulloblastoma cells.Cellular and molecular neurobiology · 2011Article
- Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma.BMC cancer · 2011Article
- Cross-platform array screening identifies COL1A2, THBS1, TNFRSF10D and UCHL1 as genes frequently silenced by methylation in melanoma.PloS one · 2011Article
- Prediction of epigenetically regulated genes in breast cancer cell lines.BMC bioinformatics · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Candidate gene investigations have indicated a significant role for epigenetic events in the pathogenesis of medulloblastoma, the most common malignant brain tumor of childhood. To assess the medulloblastoma epigenome more comprehensively, we undertook a genomewide investigation to identify genes that display evidence of methylation-dependent regulation. Expression microarray analysis of medulloblastoma cell lines following treatment with a DNA methyltransferase inhibitor revealed deregulation of multiple transcripts (3%-6% of probes per cell line). Eighteen independent genes demonstrated >3-fold reactivation in all cell lines tested. Bisulfite sequence analysis revealed dense CpG island methylation associated with transcriptional silencing for 12 of these genes. Extension of this analysis to primary tumors and the normal cerebellum revealed three major classes of epigenetically regulated genes: (1) normally methylated genes (DAZL, ZNF157, ASN) whose methylation reflects somatic patterns observed in the cerebellum, (2) X-linked genes (MSN, POU3F4, HTR2C) that show disruption of their sex-specific methylation patterns in tumors, and (3) tumor-specific methylated genes (COL1A2, S100A10, S100A6, HTATIP2, CDH1, LXN) that display enhanced methylation levels in tumors compared with the cerebellum. Detailed analysis of COL1A2 supports a key role in medulloblastoma tumorigenesis; dense biallelic methylation associated with transcriptional silencing was observed in 46 of 60 cases (77%). Moreover, COL1A2 status distinguished infant medulloblastomas of the desmoplastic histopathological subtype, indicating that distinct molecular pathogenesis may underlie these tumors and their more favorable prognosis. These data reveal a more diverse and expansive medulloblastoma epi genome than previously understood and provide strong evidence that the methylation status of specific genes may contribute to the biological subclassification of medulloblastoma.
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