Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells.
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Date
2016-06-01ICR Author
Author
Rajan, N
Andersson, MK
Sinclair, N
Fehr, A
Hodgson, K
Lord, CJ
Kazakov, DV
Vanecek, T
Ashworth, A
Stenman, G
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Skin Neoplasms
Neoplastic Syndromes, Hereditary
Oncogene Proteins, Fusion
Tumor Suppressor Proteins
Oligonucleotide Array Sequence Analysis
In Situ Hybridization, Fluorescence
Gene Expression Profiling
Sequence Analysis, DNA
Cell Proliferation
Genotype
Phenotype
Germ-Line Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Deubiquitinating Enzyme CYLD
Research team
Gene Function
Language
eng
Date accepted
2016-03-07
License start date
2016-06
Citation
The Journal of pathology, 2016, 239 (2), pp. 197 - 205
Publisher
WILEY-BLACKWELL