dc.contributor.author | Rajan, N | |
dc.contributor.author | Andersson, MK | |
dc.contributor.author | Sinclair, N | |
dc.contributor.author | Fehr, A | |
dc.contributor.author | Hodgson, K | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Kazakov, DV | |
dc.contributor.author | Vanecek, T | |
dc.contributor.author | Ashworth, A | |
dc.contributor.author | Stenman, G | |
dc.date.accessioned | 2016-09-28T14:48:05Z | |
dc.date.issued | 2016-06-01 | |
dc.identifier.citation | The Journal of pathology, 2016, 239 (2), pp. 197 - 205 | |
dc.identifier.issn | 0022-3417 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/156 | |
dc.identifier.eissn | 1096-9896 | |
dc.identifier.doi | 10.1002/path.4717 | |
dc.description.abstract | Cutaneous 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.format | Print-Electronic | |
dc.format.extent | 197 - 205 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY-BLACKWELL | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Skin Neoplasms | |
dc.subject | Neoplastic Syndromes, Hereditary | |
dc.subject | Oncogene Proteins, Fusion | |
dc.subject | Tumor Suppressor Proteins | |
dc.subject | Oligonucleotide Array Sequence Analysis | |
dc.subject | In Situ Hybridization, Fluorescence | |
dc.subject | Gene Expression Profiling | |
dc.subject | Sequence Analysis, DNA | |
dc.subject | Cell Proliferation | |
dc.subject | Genotype | |
dc.subject | Phenotype | |
dc.subject | Germ-Line Mutation | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Deubiquitinating Enzyme CYLD | |
dc.title | Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-07 | |
rioxxterms.versionofrecord | 10.1002/path.4717 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The Journal of pathology | |
pubs.issue | 2 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 239 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Lord, Christopher | |