Article: Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas

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TitleEpigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas
AuthorsJin, H6
Wang, X6
Ying, J6
Wong, AHY6
Li, H6
Lee, KY6
Srivastava, G2
Chan, ATC6
Yeo, W6
Ma, BBY6
Putti, TC1
Lung, ML5
Shen, ZY3
Xu, LY3
Langford, C4
Tao, Q6
KeywordsADAMTS18
Carcinoma
Methylation
Promoter
Tumor suppressor gene
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
CitationOncogene, 2007, v. 26 n. 53, p. 7490-7498 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.onc.1210559
AbstractTumor suppressor genes (TSGs) often locate at chromosomal regions with frequent deletions in tumors. Loss of 16q23 occurs frequently in multiple tumors, indicating the presence of critical TSGs at this locus, such as the well-studied WWOX. Herein, we found that ADAMTS18, located next to WWOX, was significantly downregulated in multiple carcinoma cell lines. No deletion of ADAMTS18 was detected with multiplex differential DNA-PCR or high-resolution 1-Mb array-based comparative genomic hybridization (CGH) analysis. Instead, methylation of the ADAMTS18 promoter CpG Island was frequently detected with methylation-specific PCR and bisulfite genome sequencing in multiple carcinoma cell lines and primary carcinomas, but not in any nontumor cell line and normal epithelial tissue. Both pharmacological and genetic demethylation dramatically induced the ADAMTS18 expression, indicating that CpG methylation directly contributes to the tumor-specific silencing of ADAMTS18. Ectopic ADAMTS18 expression led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells lacking the expression. Thus, through functional epigenetics, we identified ADAMTS18 as a novel functional tumor suppressor, being frequently inactivated epigenetically in multiple carcinomas. © 2007 Nature Publishing Group All rights reserved.
ISSN0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
DOIhttp://dx.doi.org/10.1038/sj.onc.1210559
ISI Accession Number IDWOS:000251282000010
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorJin, H
dc.contributor.authorWang, X
dc.contributor.authorYing, J
dc.contributor.authorWong, AHY
dc.contributor.authorLi, H
dc.contributor.authorLee, KY
dc.contributor.authorSrivastava, G
dc.contributor.authorChan, ATC
dc.contributor.authorYeo, W
dc.contributor.authorMa, BBY
dc.contributor.authorPutti, TC
dc.contributor.authorLung, ML
dc.contributor.authorShen, ZY
dc.contributor.authorXu, LY
dc.contributor.authorLangford, C
dc.contributor.authorTao, Q
dc.date.accessioned2012-05-29T06:13:31Z
dc.date.available2012-05-29T06:13:31Z
dc.date.issued2007
dc.description.abstractTumor suppressor genes (TSGs) often locate at chromosomal regions with frequent deletions in tumors. Loss of 16q23 occurs frequently in multiple tumors, indicating the presence of critical TSGs at this locus, such as the well-studied WWOX. Herein, we found that ADAMTS18, located next to WWOX, was significantly downregulated in multiple carcinoma cell lines. No deletion of ADAMTS18 was detected with multiplex differential DNA-PCR or high-resolution 1-Mb array-based comparative genomic hybridization (CGH) analysis. Instead, methylation of the ADAMTS18 promoter CpG Island was frequently detected with methylation-specific PCR and bisulfite genome sequencing in multiple carcinoma cell lines and primary carcinomas, but not in any nontumor cell line and normal epithelial tissue. Both pharmacological and genetic demethylation dramatically induced the ADAMTS18 expression, indicating that CpG methylation directly contributes to the tumor-specific silencing of ADAMTS18. Ectopic ADAMTS18 expression led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells lacking the expression. Thus, through functional epigenetics, we identified ADAMTS18 as a novel functional tumor suppressor, being frequently inactivated epigenetically in multiple carcinomas. © 2007 Nature Publishing Group All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationOncogene, 2007, v. 26 n. 53, p. 7490-7498 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.onc.1210559
dc.identifier.citeulike1373647
dc.identifier.doihttp://dx.doi.org/10.1038/sj.onc.1210559
dc.identifier.epage7498
dc.identifier.hkuros132779
dc.identifier.isiWOS:000251282000010
dc.identifier.issn0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
dc.identifier.issue53
dc.identifier.pmid17546048
dc.identifier.scopuseid_2-s2.0-34648817483
dc.identifier.spage7490
dc.identifier.urihttp://hdl.handle.net/10722/148525
dc.identifier.volume26
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
dc.publisher.placeUnited Kingdom
dc.relation.ispartofOncogene
dc.relation.referencesReferences in Scopus
dc.subject.meshAdam Proteins - Genetics
dc.subject.meshCell Growth Processes - Genetics
dc.subject.meshCell Line, Tumor
dc.subject.meshChromosomes, Human, Pair 16
dc.subject.meshDna Methylation
dc.subject.meshDown-Regulation
dc.subject.meshEsophageal Neoplasms - Genetics
dc.subject.meshFemale
dc.subject.meshGene Deletion
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshGene Silencing
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshHela Cells
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshNasopharyngeal Neoplasms - Genetics
dc.subject.meshNucleic Acid Hybridization
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subjectADAMTS18
dc.subjectCarcinoma
dc.subjectMethylation
dc.subjectPromoter
dc.subjectTumor suppressor gene
dc.titleEpigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas
dc.typeArticle
Author Affiliations
  1. Yong Loo Lin School of Medicine
  2. The University of Hong Kong
  3. Shantou University, Medical College (SUMC)
  4. Wellcome Trust Sanger Institute
  5. Hong Kong University of Science and Technology
  6. Chinese University of Hong Kong