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Article: Gene hypermethylation in multiple myeloma: Lessons from a cancer pathway approach

TitleGene hypermethylation in multiple myeloma: Lessons from a cancer pathway approach
Authors
Keywordsβ-catenin
5-Azacytidine
Interleukin-6
Methylation-specific polymerase chain reaction
Issue Date2008
PublisherCancer Information Group, LP. The Journal's web site is located at http://www.clinicallymphoma.com
Citation
Clinical Lymphoma And Myeloma, 2008, v. 8 n. 6, p. 331-339 How to Cite?
AbstractMultiple myeloma (MM) is an incurable plasma cell neoplasm. Pathogenesis involves upregulation of D-type cyclins and activation of oncogenes, but little is known about the role of tumor suppressor genes. Gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation. Various approaches have been used to elucidate the role of gene hypermethylation in MM, including a candidate gene approach, microarray approach for genes upregulated by hypomethylating agents, and a cancer pathway approach, which enables a comprehensive picture of the involvement of multiple tumor suppressor genes in MM. Based on the cancer pathway approach, the following data on the involvement of cell cycle control, intrinsic tumor suppressor, and cell signaling were derived. First, among the INK4 and CIP/KIP families of cyclin-dependent kinase inhibitors, only CDKN2B and CDKN2A are frequently hypermethylated. Second, methylation of SHP1 and soluble Wnt inhibitors is associated with constitutive activation of JAK/STAT and Wnt signaling. Importantly, downregulation of the signaling pathways can be restored by demethylation and re-expression of SHP1 and soluble Wnt inhibitors, which is potentially important therapeutically. Third, of the tumor suppressor genes involved in the DAPK/P14/HDM2/P53/Apaf-1 pathway, only DAPK is frequently methylated, which appeared to be an adverse prognostic factor to survival. Lastly, apart from being implicated in the progression from monoclonal gammopathy of unknown significance to MM, aberrant gene promoter methylation might also account for late disease progression in MM. Future studies are needed to delineate the biologic consequence of gene hypermethylation, the prognostic effect of gene methylation, and the possibility of hypomethylation therapy.
Persistent Identifierhttp://hdl.handle.net/10722/59137
ISSN
2009 Impact Factor: 1.13
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, Cen_HK
dc.contributor.authorKwong, Yen_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2010-05-31T03:43:36Z-
dc.date.available2010-05-31T03:43:36Z-
dc.date.issued2008en_HK
dc.identifier.citationClinical Lymphoma And Myeloma, 2008, v. 8 n. 6, p. 331-339en_HK
dc.identifier.issn1557-9190en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59137-
dc.description.abstractMultiple myeloma (MM) is an incurable plasma cell neoplasm. Pathogenesis involves upregulation of D-type cyclins and activation of oncogenes, but little is known about the role of tumor suppressor genes. Gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation. Various approaches have been used to elucidate the role of gene hypermethylation in MM, including a candidate gene approach, microarray approach for genes upregulated by hypomethylating agents, and a cancer pathway approach, which enables a comprehensive picture of the involvement of multiple tumor suppressor genes in MM. Based on the cancer pathway approach, the following data on the involvement of cell cycle control, intrinsic tumor suppressor, and cell signaling were derived. First, among the INK4 and CIP/KIP families of cyclin-dependent kinase inhibitors, only CDKN2B and CDKN2A are frequently hypermethylated. Second, methylation of SHP1 and soluble Wnt inhibitors is associated with constitutive activation of JAK/STAT and Wnt signaling. Importantly, downregulation of the signaling pathways can be restored by demethylation and re-expression of SHP1 and soluble Wnt inhibitors, which is potentially important therapeutically. Third, of the tumor suppressor genes involved in the DAPK/P14/HDM2/P53/Apaf-1 pathway, only DAPK is frequently methylated, which appeared to be an adverse prognostic factor to survival. Lastly, apart from being implicated in the progression from monoclonal gammopathy of unknown significance to MM, aberrant gene promoter methylation might also account for late disease progression in MM. Future studies are needed to delineate the biologic consequence of gene hypermethylation, the prognostic effect of gene methylation, and the possibility of hypomethylation therapy.en_HK
dc.languageengen_HK
dc.publisherCancer Information Group, LP. The Journal's web site is located at http://www.clinicallymphoma.comen_HK
dc.relation.ispartofClinical Lymphoma and Myelomaen_HK
dc.subjectβ-cateninen_HK
dc.subject5-Azacytidineen_HK
dc.subjectInterleukin-6en_HK
dc.subjectMethylation-specific polymerase chain reactionen_HK
dc.titleGene hypermethylation in multiple myeloma: Lessons from a cancer pathway approachen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1557-9190&volume=8&issue=6&spage=331&epage=9&date=2008&atitle=Gene+hypermethylation+in+multiple+myeloma:+lessons+from+a+cancer+pathway+approachen_HK
dc.identifier.emailChim, C:jcschim@hku.hken_HK
dc.identifier.emailKwong, Y:ylkwong@hku.hken_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.authorityChim, C=rp00408en_HK
dc.identifier.authorityKwong, Y=rp00358en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3816/CLM.2008.n.048en_HK
dc.identifier.scopuseid_2-s2.0-59649104770en_HK
dc.identifier.hkuros158559en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-59649104770&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue6en_HK
dc.identifier.spage331en_HK
dc.identifier.epage339en_HK
dc.identifier.isiWOS:000261462300002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChim, C=7004597253en_HK
dc.identifier.scopusauthoridKwong, Y=7102818954en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK

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