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Article: Frequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma

TitleFrequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma
Authors
KeywordsCADM1
DAL-1
Methylation
Nasal lymphoma
Tumor suppressor gene
Issue Date2009
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2009, v. 124 n. 7, p. 1572-1578 How to Cite?
AbstractNasal NK/T-cell lymphoma (NL) is a rare but clinically important entity of lymphoma. Its preferential incidence in Orientals but not Caucasians suggests possible genetic predisposition. 11q deletion is common in NL, indicating certain tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1), and its partner DAL-1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were detected in 2 NL and 4 of 8 (50%) of non-Hodgkin lymphoma (NHL) cell lines, but not in normal NK cells and normal PBMC. Absence of CADM1 protein was also detected in NL cell lines. 5-aza-20 -deoxycytidine (Aza) demethylation or genetic knockout of both DNMT1 and 3B genes restored CADM1 and DAL-1 expression. CADM1 methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly, DAL-1 was epigenetically inactivated in NL cell lines and virtually all the tumors with methylated CADM1. A significant correlation between the methylation of both genes was found (p < 0.0001). Homozygous deletion of CADM1 was detected in only 3 of 18 (17%) of tumors. The stress-response of CADM1 was abolished when its promoter becomes methylated. Our results demonstrate a frequent, predominant epigenetic silencing of CADM1 and DAL- 1 in NL, which likely play a synergic role in NL pathogenesis. © 2008 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/60577
ISSN
2014 Impact Factor: 5.085
ISI Accession Number ID
Funding AgencyGrant Number
Johns Hopkins Singapore
Chinese University of Hong Kong
University of Hong Kong10207480
Funding Information:

Grant sponsors: Johns Hopkins Singapore (A*STAR grant), Chinese University of Hong Kong. Grant sponsor: University of Hong Kong; Grant number: 10207480.

References

 

DC FieldValueLanguage
dc.contributor.authorFu, Len_HK
dc.contributor.authorGao, Zen_HK
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorTsang, YHen_HK
dc.contributor.authorGoh, HKen_HK
dc.contributor.authorGeng, Hen_HK
dc.contributor.authorShimizu, Nen_HK
dc.contributor.authorTsuchiyama, Jen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-05-31T04:14:02Z-
dc.date.available2010-05-31T04:14:02Z-
dc.date.issued2009en_HK
dc.identifier.citationInternational Journal Of Cancer, 2009, v. 124 n. 7, p. 1572-1578en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60577-
dc.description.abstractNasal NK/T-cell lymphoma (NL) is a rare but clinically important entity of lymphoma. Its preferential incidence in Orientals but not Caucasians suggests possible genetic predisposition. 11q deletion is common in NL, indicating certain tumor suppressor genes (TSGs) at this locus involved in its pathogenesis. We investigated the expression and methylation of an 11q23.2 TSG, CADM1 (or TSLC1), and its partner DAL-1 (or EPB41L3) in NL. Methylation and silencing of CADM1 were detected in 2 NL and 4 of 8 (50%) of non-Hodgkin lymphoma (NHL) cell lines, but not in normal NK cells and normal PBMC. Absence of CADM1 protein was also detected in NL cell lines. 5-aza-20 -deoxycytidine (Aza) demethylation or genetic knockout of both DNMT1 and 3B genes restored CADM1 and DAL-1 expression. CADM1 methylation was further detected in 36 of 45 (80%) of NL tumors. Concomitantly, DAL-1 was epigenetically inactivated in NL cell lines and virtually all the tumors with methylated CADM1. A significant correlation between the methylation of both genes was found (p < 0.0001). Homozygous deletion of CADM1 was detected in only 3 of 18 (17%) of tumors. The stress-response of CADM1 was abolished when its promoter becomes methylated. Our results demonstrate a frequent, predominant epigenetic silencing of CADM1 and DAL- 1 in NL, which likely play a synergic role in NL pathogenesis. © 2008 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectCADM1en_HK
dc.subjectDAL-1en_HK
dc.subjectMethylationen_HK
dc.subjectNasal lymphomaen_HK
dc.subjectTumor suppressor geneen_HK
dc.titleFrequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=124&issue=7&spage=1572&epage=1578&date=2008&atitle=Frequent+concomitant+epigenetic+silencing+of+the+stress-responsive+tumor+suppressor+gene+CADM1,+and+its+interacting+partner+DAL-1+in+nasal+NK/T-cell+lymphomaen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.24123en_HK
dc.identifier.scopuseid_2-s2.0-61449219037en_HK
dc.identifier.hkuros154352en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-61449219037&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume124en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1572en_HK
dc.identifier.epage1578en_HK
dc.identifier.isiWOS:000263804900009-
dc.publisher.placeUnited Statesen_HK

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