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Article: Alterations of RAS signalling in Chinese multiple myeloma patients: Absent BRAF and rare RAS mutations, but frequent inactivation of RASSF1A by transcriptional silencing or expression of a non-functional variant transcript

TitleAlterations of RAS signalling in Chinese multiple myeloma patients: Absent BRAF and rare RAS mutations, but frequent inactivation of RASSF1A by transcriptional silencing or expression of a non-functional variant transcript
Authors
Issue Date2003
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJH
Citation
British Journal Of Haematology, 2003, v. 123 n. 4, p. 637-645 How to Cite?
AbstractThe methylation status, mutation and expression of RASSF1A, and mutations of RAS and BRAF were studied in 52 patients with multiple myeloma (MM), one plasma cell leukaemia (PCL) patient and four MM-derived cell lines. Aberrant methylation of RASSF1A was found in nine of 32 MM patients and in one of four MM cell lines (U266), where the associated loss of transcription was reversible by demethylation treatment. RASSF1A transcription was further investigated on anti-CD138-sorted plasma cell-enriched bone marrow samples from 10 MM, one PCL and three reactive plasmacytosis patients. While the wild-type RASSF1A transcript was detected in all three reactive plasmacytosis and the PCL samples, we found no detectable wild-type transcripts in six of 10 MM samples studied. In two MM samples, only the non-functional variant transcript was detected, whereas the other four showed loss of transcription. In great contrast to western data, RAS mutations were identified in only four of 31 (13%) MM patients. While no RASSF1A or BRAF mutation (V599E) was detected in any of the primary MM studied (n = 21), the latter was found in the U266 cell line. Taken together, these data indicate that alterations of RAS signalling are critical in MM pathogenesis. In our current studies of Chinese MM patients, these alterations involved frequent RASSF1A inactivation (60%) as a result of transcriptional silencing or expression of a non-functional variant transcript.
Persistent Identifierhttp://hdl.handle.net/10722/148365
ISSN
2015 Impact Factor: 5.401
2015 SCImago Journal Rankings: 2.313
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNg, MHLen_US
dc.contributor.authorLau, KMen_US
dc.contributor.authorWong, WSen_US
dc.contributor.authorTo, KWen_US
dc.contributor.authorCheng, SHen_US
dc.contributor.authorTsang, KSen_US
dc.contributor.authorChan, NPHen_US
dc.contributor.authorKho, BCSen_US
dc.contributor.authorLo, KWen_US
dc.contributor.authorTong, JHMen_US
dc.contributor.authorLam, CWen_US
dc.contributor.authorChan, JCWen_US
dc.date.accessioned2012-05-29T06:12:30Z-
dc.date.available2012-05-29T06:12:30Z-
dc.date.issued2003en_US
dc.identifier.citationBritish Journal Of Haematology, 2003, v. 123 n. 4, p. 637-645en_US
dc.identifier.issn0007-1048en_US
dc.identifier.urihttp://hdl.handle.net/10722/148365-
dc.description.abstractThe methylation status, mutation and expression of RASSF1A, and mutations of RAS and BRAF were studied in 52 patients with multiple myeloma (MM), one plasma cell leukaemia (PCL) patient and four MM-derived cell lines. Aberrant methylation of RASSF1A was found in nine of 32 MM patients and in one of four MM cell lines (U266), where the associated loss of transcription was reversible by demethylation treatment. RASSF1A transcription was further investigated on anti-CD138-sorted plasma cell-enriched bone marrow samples from 10 MM, one PCL and three reactive plasmacytosis patients. While the wild-type RASSF1A transcript was detected in all three reactive plasmacytosis and the PCL samples, we found no detectable wild-type transcripts in six of 10 MM samples studied. In two MM samples, only the non-functional variant transcript was detected, whereas the other four showed loss of transcription. In great contrast to western data, RAS mutations were identified in only four of 31 (13%) MM patients. While no RASSF1A or BRAF mutation (V599E) was detected in any of the primary MM studied (n = 21), the latter was found in the U266 cell line. Taken together, these data indicate that alterations of RAS signalling are critical in MM pathogenesis. In our current studies of Chinese MM patients, these alterations involved frequent RASSF1A inactivation (60%) as a result of transcriptional silencing or expression of a non-functional variant transcript.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/BJHen_US
dc.relation.ispartofBritish Journal of Haematologyen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshChinaen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDna Mutational Analysis - Methodsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMultiple Myeloma - Metabolismen_US
dc.subject.meshNeoplasm Proteins - Geneticsen_US
dc.subject.meshOncogene Proteins - Geneticsen_US
dc.subject.meshProto-Oncogene Proteins B-Rafen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSequence Analysis, Dna - Methodsen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTumor Suppressor Proteinsen_US
dc.subject.meshRas Proteins - Metabolismen_US
dc.titleAlterations of RAS signalling in Chinese multiple myeloma patients: Absent BRAF and rare RAS mutations, but frequent inactivation of RASSF1A by transcriptional silencing or expression of a non-functional variant transcripten_US
dc.typeArticleen_US
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_US
dc.identifier.authorityLam, CW=rp00260en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1365-2141.2003.04664.xen_US
dc.identifier.pmid14616967-
dc.identifier.scopuseid_2-s2.0-0345392554en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0345392554&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume123en_US
dc.identifier.issue4en_US
dc.identifier.spage637en_US
dc.identifier.epage645en_US
dc.identifier.isiWOS:000186415600010-
dc.publisher.placeUnited Kingdomen_US

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