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Article: Specific patterns of gene methylation in natural killer cell lymphomas: p73 is consistently involved

TitleSpecific patterns of gene methylation in natural killer cell lymphomas: p73 is consistently involved
Authors
Issue Date2002
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal Of Pathology, 2002, v. 160 n. 1, p. 59-66 How to Cite?
AbstractAberrant methylation of promoter CpG regions is a putative mechanism whereby tumor suppressor genes are inactivated. We used a candidate gene approach to investigate the patterns and significance of this epigenetic change in natural killer (NK) cell malignancies. Thirty-three patients were studied for promoter methylation in five putative tumor suppressor genes by methylation-specific polymerase chain reaction (MSP), which has a sensitivity of 10 -3. The p73 gene was methylated in 94% of cases, a frequency that is the highest known for any human malignancy. In the NK cell lymphoma line NK92, p73 was also completely methylated, and the p73 transcript was correspondingly not detectable by quantitative polymerase chain reaction. Treatment of the cell line with 5-azacytidine, a demethylation reagent, led to demethylation of the p73 promoter and reinduction of p73 gene expression. These results suggested that promoter CpG methylation might be an important mechanism in suppressing p73 gene expression in NK cells. Other methylated genes included bMLH1 (63%), p16 (63%), p15 (48%), and RARβ (47%). Methylation of two or more genes occurred in 88% of cases. With promoter methylation as a molecular marker, MSP identified two cases of occult marrow metastasis. Interestingly, the primary tumor and metastasis showed different methylation patterns, implying that separate clonal evolutions might have occurred at these sites. Furthermore, MSP also identified tumor infiltration in random oropharyngeal biopsies in a case where histological examination could not show evidence of tumor involvement. We conclude that NK cell malignancies show a specific pattern of promoter methylation, with p73 being consistently involved. These results suggest that p73 may be an important target in the neoplastic transformation of NK cells, and the demonstration of its methylation may serve as a potential molecular tool for NK cell lymphoma detection.
Persistent Identifierhttp://hdl.handle.net/10722/49115
ISSN
2015 Impact Factor: 4.206
2015 SCImago Journal Rankings: 2.653
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSiu, LLPen_HK
dc.contributor.authorChan, JKCen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorKwong, YLen_HK
dc.date.accessioned2008-06-12T06:34:45Z-
dc.date.available2008-06-12T06:34:45Z-
dc.date.issued2002en_HK
dc.identifier.citationAmerican Journal Of Pathology, 2002, v. 160 n. 1, p. 59-66en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49115-
dc.description.abstractAberrant methylation of promoter CpG regions is a putative mechanism whereby tumor suppressor genes are inactivated. We used a candidate gene approach to investigate the patterns and significance of this epigenetic change in natural killer (NK) cell malignancies. Thirty-three patients were studied for promoter methylation in five putative tumor suppressor genes by methylation-specific polymerase chain reaction (MSP), which has a sensitivity of 10 -3. The p73 gene was methylated in 94% of cases, a frequency that is the highest known for any human malignancy. In the NK cell lymphoma line NK92, p73 was also completely methylated, and the p73 transcript was correspondingly not detectable by quantitative polymerase chain reaction. Treatment of the cell line with 5-azacytidine, a demethylation reagent, led to demethylation of the p73 promoter and reinduction of p73 gene expression. These results suggested that promoter CpG methylation might be an important mechanism in suppressing p73 gene expression in NK cells. Other methylated genes included bMLH1 (63%), p16 (63%), p15 (48%), and RARβ (47%). Methylation of two or more genes occurred in 88% of cases. With promoter methylation as a molecular marker, MSP identified two cases of occult marrow metastasis. Interestingly, the primary tumor and metastasis showed different methylation patterns, implying that separate clonal evolutions might have occurred at these sites. Furthermore, MSP also identified tumor infiltration in random oropharyngeal biopsies in a case where histological examination could not show evidence of tumor involvement. We conclude that NK cell malignancies show a specific pattern of promoter methylation, with p73 being consistently involved. These results suggest that p73 may be an important target in the neoplastic transformation of NK cells, and the demonstration of its methylation may serve as a potential molecular tool for NK cell lymphoma detection.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.relation.ispartofAmerican Journal of Pathologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshIntercellular Signaling Peptides and Proteins - metabolismen_HK
dc.subject.meshLeptin - metabolismen_HK
dc.subject.meshLiver Cirrhosis - metabolism - pathologyen_HK
dc.subject.meshObesity - metabolismen_HK
dc.subject.meshActins - metabolismen_HK
dc.titleSpecific patterns of gene methylation in natural killer cell lymphomas: p73 is consistently involveden_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9440&volume=160&issue=1&spage=59&epage=66&date=2002&atitle=Specific+patterns+of+gene+methylation+in+natural+killer+cell+lymphomas:+p73+is+consistently+involveden_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid11786399-
dc.identifier.pmcidPMC1867120en_HK
dc.identifier.scopuseid_2-s2.0-0036141154en_HK
dc.identifier.hkuros67808-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036141154&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume160en_HK
dc.identifier.issue1en_HK
dc.identifier.spage59en_HK
dc.identifier.epage66en_HK
dc.identifier.isiWOS:000173231700009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSiu, LLP=35574705900en_HK
dc.identifier.scopusauthoridChan, JKC=26430517500en_HK
dc.identifier.scopusauthoridWong, KF=7404759860en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK

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