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Article: Frequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphoma

TitleFrequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphoma
Authors
KeywordsCell cycle
Follicular lymphoma
Hypermethylation
Mantle cell lymphoma
p15
p16
Rb1
Issue Date2007
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/humpath
Citation
Human Pathology, 2007, v. 38 n. 12, p. 1849-1857 How to Cite?
AbstractDysregulation of cell cycle control is an important mechanism in carcinogenesis. Gene promoter hypermethylation is an alternative mechanism of gene inactivation. We analyzed the methylation status of the tumor suppressor components of the INK4/Rb pathway in mantle cell lymphoma and follicular lymphoma by methylation-specific polymerase chain reaction for p15, p16, p18, and Rb1 in 23 mantle cell lymphoma and 30 follicular lymphoma cases and lymphoma cell lines. The methylation-specific polymerase chain reaction results showed that in mantle cell lymphoma, frequent p16 (82%) but infrequent p15 (8.7%) or Rb1 (17.4%) hypermethylation occurred, with p16 and Rb1 hypermethylation being mutually exclusive (P = .01). In follicular lymphoma, frequent hypermethylation of p15 (36.7%), p16 (56.7%), and Rb1 (43.3%) occurred, with p15 and Rb1 hypermethylation being mutually exclusive (P = .05). Concurrent methylation of p15 and p16 occurred in 26.7% of patients with follicular lymphoma and 8.7% of patients with mantle cell lymphoma. Compared with mantle cell lymphoma, there was more frequent p15 (P = .025) hypermethylation but comparable Rb1 (P = .07) and p16 (P = .07) hypermethylation in follicular lymphoma. In a patient with follicular lymphoma with sequential biopsies, Rb1 was unmethylated and expressed at diagnosis but became methylated and down-regulated at relapse. Moreover, methylation analysis of these 4 genes in an additional 8 patients with grade I follicular lymphoma showed that Rb, but not the other genes, was preferentially methylated in grade II (P = .03). In summary, most patients with mantle cell lymphoma and follicular lymphoma had epigenetic aberrations targeting the INK4/Rb pathway. There is more frequent p16 hypermethylation in mantle cell lymphoma and p15 or Rb1 hypermethylation in follicular lymphoma. The role of Rb methylation in disease or histologic transformation in follicular lymphoma warrants further study. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/78036
ISSN
2015 Impact Factor: 2.791
2015 SCImago Journal Rankings: 1.363
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorLoong, Fen_HK
dc.contributor.authorLam, WWen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.date.accessioned2010-09-06T07:38:28Z-
dc.date.available2010-09-06T07:38:28Z-
dc.date.issued2007en_HK
dc.identifier.citationHuman Pathology, 2007, v. 38 n. 12, p. 1849-1857en_HK
dc.identifier.issn0046-8177en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78036-
dc.description.abstractDysregulation of cell cycle control is an important mechanism in carcinogenesis. Gene promoter hypermethylation is an alternative mechanism of gene inactivation. We analyzed the methylation status of the tumor suppressor components of the INK4/Rb pathway in mantle cell lymphoma and follicular lymphoma by methylation-specific polymerase chain reaction for p15, p16, p18, and Rb1 in 23 mantle cell lymphoma and 30 follicular lymphoma cases and lymphoma cell lines. The methylation-specific polymerase chain reaction results showed that in mantle cell lymphoma, frequent p16 (82%) but infrequent p15 (8.7%) or Rb1 (17.4%) hypermethylation occurred, with p16 and Rb1 hypermethylation being mutually exclusive (P = .01). In follicular lymphoma, frequent hypermethylation of p15 (36.7%), p16 (56.7%), and Rb1 (43.3%) occurred, with p15 and Rb1 hypermethylation being mutually exclusive (P = .05). Concurrent methylation of p15 and p16 occurred in 26.7% of patients with follicular lymphoma and 8.7% of patients with mantle cell lymphoma. Compared with mantle cell lymphoma, there was more frequent p15 (P = .025) hypermethylation but comparable Rb1 (P = .07) and p16 (P = .07) hypermethylation in follicular lymphoma. In a patient with follicular lymphoma with sequential biopsies, Rb1 was unmethylated and expressed at diagnosis but became methylated and down-regulated at relapse. Moreover, methylation analysis of these 4 genes in an additional 8 patients with grade I follicular lymphoma showed that Rb, but not the other genes, was preferentially methylated in grade II (P = .03). In summary, most patients with mantle cell lymphoma and follicular lymphoma had epigenetic aberrations targeting the INK4/Rb pathway. There is more frequent p16 hypermethylation in mantle cell lymphoma and p15 or Rb1 hypermethylation in follicular lymphoma. The role of Rb methylation in disease or histologic transformation in follicular lymphoma warrants further study. © 2007 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/humpathen_HK
dc.relation.ispartofHuman Pathologyen_HK
dc.subjectCell cycleen_HK
dc.subjectFollicular lymphomaen_HK
dc.subjectHypermethylationen_HK
dc.subjectMantle cell lymphomaen_HK
dc.subjectp15en_HK
dc.subjectp16en_HK
dc.subjectRb1en_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p15 - geneticsen_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p16 - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshEpigenesis, Geneticen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLymphoma, Follicular - genetics - pathologyen_HK
dc.subject.meshLymphoma, Mantle-Cell - genetics - pathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshRetinoblastoma Protein - geneticsen_HK
dc.titleFrequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0046-8177&volume=38&issue=12&spage=1849&epage=57&date=2007&atitle=Frequent+epigenetic+inactivation+of+Rb1+in+addition+to+p15+and+p16+in+mantle+cell+and+follicular+lymphomaen_HK
dc.identifier.emailChim, CS:jcschim@hku.hken_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.humpath.2007.05.009en_HK
dc.identifier.pmid17900658-
dc.identifier.scopuseid_2-s2.0-36549037146en_HK
dc.identifier.hkuros150421en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36549037146&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume38en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1849en_HK
dc.identifier.epage1857en_HK
dc.identifier.isiWOS:000251582900016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridWong, KY=7404758500en_HK
dc.identifier.scopusauthoridLoong, F=6602794154en_HK
dc.identifier.scopusauthoridLam, WW=7203022037en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK

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