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Article: Epigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor

TitleEpigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor
Authors
KeywordsDLC-1
Epigenetics
Hypermethylation
Medulloblastoma
Supratentorial primitive neuroectodermal tumor
Transcriptional silencing
Issue Date2005
Citation
Human Pathology, 2005, v. 36, n. 1, p. 36-43 How to Cite?
AbstractSupratentorial primitive neuroectodermal tumors (SPNETs) and medulloblastomas (MBs) are histologically similar intracranial tumors found in different anatomic locations of the brain. Our group has previously demonstrated that loss of chromosome 8p is a frequent event in MBs. The aim of this study was to evaluate whether DLC-1, a newly identified tumor-suppressor gene on chromosome 8p22, is involved in the tumorigenesis of MBs and the histologically similar SPNETs. We first assessed for alterations of gene expression in microdissected tumors and detected lack of DLC-1 transcript in 1 of 9 MBs (case M44) and 1 of 3 SPNETs (case M1). Neither somatic base substitutions nor homozygous deletion were found in tumors without DLC-1 transcript. We then explored the possibility of hypermethylation of the CpG island in DLC-1 as the mechanism of suppressed expression. Methylation-specific polymerase chain reaction revealed promotor hypermethylation of DLC-1 in M1 but not in M44. Bisulfite sequencing further verified a densely methylated pattern of 35 CpG sites studied in M1 that were not found in normal brain, indicating that inactivation of DLC-1 by hypermethylation is involved in SPNET. Based on this finding, we examined an additional 20 MBs, 8 SPNETs, and 4 MB and 2 SPNET cell lines for hypermethylation of the CpG island of DLC-1, finding that none of these samples exhibited DLC-1 methylation. In conclusion, our results demonstrate that transcriptional silencing of DLC-1 through promoter hypermethylation may contribute to tumorigenesis in a subset of SPNETs, and that loss of DLC-1 expression in MBs may be related to mechanisms other than promoter hypermethylation, genomic deletion, and mutation. © 2005 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/325086
ISSN
2023 Impact Factor: 2.7
2023 SCImago Journal Rankings: 0.936
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPang, Jesse Chung Sean-
dc.contributor.authorChang, Qing-
dc.contributor.authorChung, Yuk Fei-
dc.contributor.authorTeo, Jennifer Gek Choo-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorZhou, Liang Fu-
dc.contributor.authorKong, Xiangyin-
dc.contributor.authorNg, Ho Keung-
dc.date.accessioned2023-02-27T07:29:36Z-
dc.date.available2023-02-27T07:29:36Z-
dc.date.issued2005-
dc.identifier.citationHuman Pathology, 2005, v. 36, n. 1, p. 36-43-
dc.identifier.issn0046-8177-
dc.identifier.urihttp://hdl.handle.net/10722/325086-
dc.description.abstractSupratentorial primitive neuroectodermal tumors (SPNETs) and medulloblastomas (MBs) are histologically similar intracranial tumors found in different anatomic locations of the brain. Our group has previously demonstrated that loss of chromosome 8p is a frequent event in MBs. The aim of this study was to evaluate whether DLC-1, a newly identified tumor-suppressor gene on chromosome 8p22, is involved in the tumorigenesis of MBs and the histologically similar SPNETs. We first assessed for alterations of gene expression in microdissected tumors and detected lack of DLC-1 transcript in 1 of 9 MBs (case M44) and 1 of 3 SPNETs (case M1). Neither somatic base substitutions nor homozygous deletion were found in tumors without DLC-1 transcript. We then explored the possibility of hypermethylation of the CpG island in DLC-1 as the mechanism of suppressed expression. Methylation-specific polymerase chain reaction revealed promotor hypermethylation of DLC-1 in M1 but not in M44. Bisulfite sequencing further verified a densely methylated pattern of 35 CpG sites studied in M1 that were not found in normal brain, indicating that inactivation of DLC-1 by hypermethylation is involved in SPNET. Based on this finding, we examined an additional 20 MBs, 8 SPNETs, and 4 MB and 2 SPNET cell lines for hypermethylation of the CpG island of DLC-1, finding that none of these samples exhibited DLC-1 methylation. In conclusion, our results demonstrate that transcriptional silencing of DLC-1 through promoter hypermethylation may contribute to tumorigenesis in a subset of SPNETs, and that loss of DLC-1 expression in MBs may be related to mechanisms other than promoter hypermethylation, genomic deletion, and mutation. © 2005 Elsevier Inc. All rights reserved.-
dc.languageeng-
dc.relation.ispartofHuman Pathology-
dc.subjectDLC-1-
dc.subjectEpigenetics-
dc.subjectHypermethylation-
dc.subjectMedulloblastoma-
dc.subjectSupratentorial primitive neuroectodermal tumor-
dc.subjectTranscriptional silencing-
dc.titleEpigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.humpath.2004.09.021-
dc.identifier.pmid15712180-
dc.identifier.scopuseid_2-s2.0-13444261160-
dc.identifier.volume36-
dc.identifier.issue1-
dc.identifier.spage36-
dc.identifier.epage43-
dc.identifier.isiWOS:000227086900007-

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