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dc.contributor.authorRajan, N
dc.contributor.authorAndersson, MK
dc.contributor.authorSinclair, N
dc.contributor.authorFehr, A
dc.contributor.authorHodgson, K
dc.contributor.authorLord, CJ
dc.contributor.authorKazakov, DV
dc.contributor.authorVanecek, T
dc.contributor.authorAshworth, A
dc.contributor.authorStenman, G
dc.date.accessioned2016-09-28T14:48:05Z
dc.date.issued2016-06
dc.identifier.citationThe Journal of pathology, 2016, 239 (2), pp. 197 - 205
dc.identifier.issn0022-3417
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/156
dc.identifier.eissn1096-9896
dc.identifier.doi10.1002/path.4717
dc.description.abstractCutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromas is seen in patients with Brooke-Spiegler syndrome, who carry germline mutations in the tumour suppressor gene CYLD. Previous studies of inherited cylindromas have highlighted the frequent presence of bi-allelic truncating CYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas express either MYB-NFIB fusion transcripts or show evidence of MYB activation in the absence of such fusions. Here, we investigated inherited cylindromas from several families with germline CYLD mutations for the presence of MYB activation. Strikingly, none of the inherited CYLD-defective (n = 23) tumours expressed MYB-NFIB fusion transcripts. However, MYB expression was increased in the majority of tumours (69%) and global gene expression analysis revealed that well-established MYB target genes were up-regulated in CYLD-defective tumours. Moreover, knock-down of MYB expression caused a significant reduction in cylindroma cell proliferation, suggesting that MYB is also a key player and oncogenic driver in inherited cylindromas. Taken together, our findings suggest molecular heterogeneity in the pathogenesis of sporadic and inherited cutaneous cylindromas, with convergence on MYB activation. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
dc.formatPrint-Electronic
dc.format.extent197 - 205
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectSkin Neoplasms
dc.subjectNeoplastic Syndromes, Hereditary
dc.subjectOncogene Proteins, Fusion
dc.subjectTumor Suppressor Proteins
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectGene Expression Profiling
dc.subjectSequence Analysis, DNA
dc.subjectCell Proliferation
dc.subjectGenotype
dc.subjectPhenotype
dc.subjectGerm-Line Mutation
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectDeubiquitinating Enzyme CYLD
dc.titleOverexpression of MYB drives proliferation of CYLD-defective cylindroma cells.
dc.typeJournal Article
dcterms.dateAccepted2016-03-07
rioxxterms.versionofrecord10.1002/path.4717
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Journal of pathology
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume239
pubs.embargo.termsNot known
icr.researchteamGene Functionen_US
dc.contributor.icrauthorLord, Christopheren


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