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

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TitleFrequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma
AuthorsFu, L4
Gao, Z1
Zhang, X1 5
Tsang, YH4
Goh, HK4
Geng, H8
Shimizu, N3
Tsuchiyama, J7
Srivastava, G2
Tao, Q4 6 8
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
CitationInternational Journal Of Cancer, 2009, v. 124 n. 7, p. 1572-1578 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.24123
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.
ISSN0020-7136
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
DOIhttp://dx.doi.org/10.1002/ijc.24123
ISI Accession Number IDWOS:000263804900009
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.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorFu, L
dc.contributor.authorGao, Z
dc.contributor.authorZhang, X
dc.contributor.authorTsang, YH
dc.contributor.authorGoh, HK
dc.contributor.authorGeng, H
dc.contributor.authorShimizu, N
dc.contributor.authorTsuchiyama, J
dc.contributor.authorSrivastava, G
dc.contributor.authorTao, Q
dc.date.accessioned2010-05-31T04:14:02Z
dc.date.available2010-05-31T04:14:02Z
dc.date.issued2009
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationInternational Journal Of Cancer, 2009, v. 124 n. 7, p. 1572-1578 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.24123
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.24123
dc.identifier.epage1578
dc.identifier.hkuros154352
dc.identifier.isiWOS:000263804900009
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.

dc.identifier.issn0020-7136
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
dc.identifier.issue7
dc.identifier.openurl
dc.identifier.scopuseid_2-s2.0-61449219037
dc.identifier.spage1572
dc.identifier.urihttp://hdl.handle.net/10722/60577
dc.identifier.volume124
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
dc.publisher.placeUnited States
dc.relation.ispartofInternational Journal of Cancer
dc.relation.referencesReferences in Scopus
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.
dc.subjectCADM1
dc.subjectDAL-1
dc.subjectMethylation
dc.subjectNasal lymphoma
dc.subjectTumor suppressor gene
dc.titleFrequent concomitant epigenetic silencing of the stress-responsive tumor suppressor gene CADM1, and its interacting partner DAL-1 in nasal NK/T-cell lymphoma
dc.typeArticle
Author Affiliations
  1. Peking University Health Science Center
  2. The University of Hong Kong
  3. Dental University
  4. Johns Hopkins Singapore
  5. Yan'an University
  6. The Johns Hopkins School of Medicine
  7. Kawasaki Medical College
  8. Chinese University of Hong Kong