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dc.contributor.authorHesson, Luke Ben
dc.contributor.authorDunwell, Thomas Len
dc.contributor.authorCooper, Wendyen
dc.contributor.authorCatchpoole, Danielen
dc.contributor.authorBrini, Anna Ten
dc.contributor.authorChiaramonte, Raffaellaen
dc.contributor.authorGriffiths, Mikeen
dc.contributor.authorChalmers, Andrew Den
dc.contributor.authorMaher, Eamonnen
dc.contributor.authorLatif, Faridaen
dc.date.accessioned2011-06-13T15:29:19Z
dc.date.available2011-06-13T15:29:19Z
dc.date.issued2009-07-01en
dc.identifier.issn1476-4598
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/237574
dc.description.abstractAbstract Background The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples. Results COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC). Conclusion This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.
dc.languageEnglishen
dc.language.isoen
dc.titleThe novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemiasen
dc.typeArticle
dc.date.updated2011-06-13T15:29:19Z
dc.description.versionRIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.en
dc.rights.holderHesson et al.; licensee BioMed Central Ltd.
prism.publicationDate2009en
dcterms.dateAccepted2009-07-01en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2009-07-01en
dc.contributor.orcidCooper, Wendy [0000-0003-3416-9982]
dc.contributor.orcidMaher, Eamonn [0000-0002-6226-6918]
dc.identifier.eissn1476-4598
rioxxterms.typeJournal Article/Reviewen


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