Abstract
Cutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromascs seen in patients with Brooke-Spiegler syndrome, who carry germline mutations in the tumour suppressor genecCYLD.
Previous studies of inherited cylindromas have highlighted the frequent presence of bi-allelic truncatingcCYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas expressceither MYB-NFIB fusionctranscripts 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 ofcMYB activation. Strikingly, none of the inherited CYLD-defective (n = 23) tumours expressed MYB-NFIB fusionctranscripts.cHowever, MYB expression was increased in the majority of tumours (69%) and global gene expressioncanalysis revealed that well-established MYB target genes were up-regulated in CYLD-defective tumours.
Moreover,cknock-down of MYB expression caused a significant reduction in cylindroma cell proliferation, suggesting thatcMYB is also a key player and oncogenic driver incinherited cylindromas. Taken together, our findings suggest molecular heterogeneity in the pathogenesis of sporadic and inherited cutaneous cylindromas, with convergence on MYB activation.