Cutaneous cylindroma: it's all about MYB

Abstract

Cutaneous cylindroma is a rare benign tumour that occasionally turns into malignant cylindrocarcinoma. The AQ2 cancer can be sporadic or emerge in the context of Brooke–Spiegler syndrome (BSS), an inheritable condition characterized by mutation of the gene CYLD, encoding a tumour suppressor protein that controls the activity of the transcription factor NF-kB. Sporadic cylindromas present histological features shared with adenoid cystic carcinoma (ACC), a head and neck cancer originating from salivary or other exocrine glands. Like ACCs, sporadic cylindromas express, although at lower frequency, the aberrant fusion transcript MYB–NFIB. In a paper recently published in the Journal of Pathology , the research teams led by Neil Rajan and Goran Stenman demonstrate that CYLD-defective cyclindromas in BSS patients are negative for the MYB–NFIB fusion. Only the wild-type MYB oncoprotein is activated in the majority of these tumours. RNA interference studies in cells derived from BSS patients indicate that ablating MYB expression results in a striking reduction of cylindroma cell proliferation, suggesting that MYB plays a pivotal role in the biology of this cancer. The take-home message of the study is that activation of MYB, in its wild-type form or fusion derivatives, is a common feature of spontaneous and hereditary cylindromas, constituting a potentially actionable therapeutic target.