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dc.contributor.authorAstuti, D
dc.contributor.authorMorris, M
dc.contributor.authorKrona, C
dc.contributor.authorAbel, F
dc.contributor.authorGentle, D
dc.contributor.authorMartinsson, T
dc.contributor.authorKogner, P
dc.contributor.authorNeumann, HPH
dc.contributor.authorVoutilainen, R
dc.contributor.authorEng, C
dc.contributor.authorRustin, P
dc.contributor.authorLatif, F
dc.contributor.authorMaher, ER
dc.date.accessioned2019-05-31T11:27:02Z
dc.date.available2019-05-31T11:27:02Z
dc.date.issued2004-10-26
dc.identifier.citationAstuti, D., Morris, M., Krona, C., Abel, F., Gentle, D., Martinsson, T., Kogner, P., Neumann, H. P. H., Voutilainen, R., Eng, C., Rustin, P., Latif, F. and Maher, E. R. (2004) Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma, British Journal of Cancer (2004) 91, pp. 1835-1841.en
dc.identifier.pmid15505628
dc.identifier.doi10.1038/sj.bjc.6602202en
dc.identifier.urihttp://hdl.handle.net/2436/622387
dc.description.abstractGermline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence, to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we performed mutation analysis in 46 primary neuroblastomas by direct sequencing, but did not identify germline or somatic SDHB mutations. As TSGs such as RASSF1A are frequently inactivated by promoter region hypermethylation, we designed a methylation-sensitive PCR-based assay to detect SDHB promoter region methylation. In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated (and unmethylated) alleles were detected. Although promoter region methylation was also detected in two neuroblastoma cell lines, this was not associated with silencing of SDHB expression, and treatment with a demethylating agent (5-azacytidine) did not increase SDH activity. These findings suggest that although germline SDHB mutations are an important cause of phaeochromocytoma susceptibility, somatic inactivation of SDHB does not have a major role in sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in neuroblastoma and phaeochromocytoma. © 2004 Cancer Research UK.en
dc.description.sponsorshipThis work is supported by the British Heart Foundation (DA, FL, EM), Cancer Research UK (MM, FL, EM), Swedish Cancer Society, Swedish Children's Cancer Foundation (TM, PK), Deutsche Forchungsgemeinschaft Grant NE 571/5-2 and the Deutsche Krebshilfe Grant 70-3313-Ne 1 (HPH) and P30CA16058 from the National Cancer Institute, Bethesda, MD, USA (to The Ohio State University Comprehensive Cancer Center). CE is a recipient of the Doris Duke Distinguished Clinical Scientist Award.en
dc.formatapplication/PDFen
dc.languageeng
dc.language.isoenen
dc.publisherSpringer Natureen
dc.subjectCell Line, Tumoren
dc.subjectNeural Cresten
dc.subjectHumansen
dc.subjectNeuroblastomaen
dc.subjectPheochromocytomaen
dc.subjectSuccinate Dehydrogenaseen
dc.subjectIron-Sulfur Proteinsen
dc.subjectProtein Subunitsen
dc.subjectDNA Methylationen
dc.subjectGene Silencingen
dc.subjectBase Sequenceen
dc.subjectMutationen
dc.subjectLoss of Heterozygosityen
dc.subjectMolecular Sequence Dataen
dc.subjectPromoter Regions, Geneticen
dc.titleInvestigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastomaen
dc.typeJournal articleen
dc.identifier.eissn1532-1827
dc.identifier.journalBritish Journal of Canceren
dc.date.updated2019-05-21T15:00:12Z
dc.contributor.institutionSection of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham B15 2TT, UK.
pubs.place-of-publicationEngland
dc.date.accepted2004-09-02
rioxxterms.funderUniversity of Wolverhamptonen
rioxxterms.identifier.projectP30CA16058en
rioxxterms.identifier.projectP30 CA016058en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-sa/4.0/en
rioxxterms.licenseref.startdate2019-05-31en
dc.source.volume91
dc.source.issue10
dc.source.beginpage1835
dc.source.endpage1841
dc.description.versionPublished version
refterms.dateFCD2019-05-31T11:26:44Z
refterms.versionFCDVoR
refterms.dateFOA2019-05-31T11:27:02Z


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