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Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells

Artikel i vetenskaplig tidskrift
Författare N. Rajan
Mattias K Andersson
N. Sinclair
Andre Fehr
K. Hodgson
C. J. Lord
D. V. Kazakov
T. Vanecek
A. Ashworth
Göran Stenman
Publicerad i Journal of Pathology
Volym 239
Nummer/häfte 2
Sidor 197-205
ISSN 0022-3417
Publiceringsår 2016
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Sahlgrenska Cancer Center
Sidor 197-205
Språk en
Länkar dx.doi.org/10.1002/path.4717
Ämnesord cylindroma, adenoid cystic carcinoma, germline mutation, CYLD, MYB, MYB-NFIB, gene fusion, adenoid cystic carcinoma, brooke-spiegler syndrome, tumor-suppressor, gene, gland, spiradenocylindroma, spiradenoma, mutations, neoplasms, germline, families, Oncology, Pathology
Ämneskategorier Cancer och onkologi

Sammanfattning

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. (C) 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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