Cutaneous cylindroma: it's all about MYB

Area of Science:

• Oncology
• Genetics
• Cancer Biology

Background:

• Cutaneous cylindroma is a rare benign tumor with malignant potential (cylindrocarcinoma).
• Brooke-Spiegler syndrome (BSS) involves CYLD gene mutations, affecting NF-kB signaling.
• Sporadic cylindromas share features with adenoid cystic carcinoma (ACC), including MYB-NFIB fusion transcripts.

Purpose of the Study:

• To investigate the role of MYB oncoprotein in sporadic and BSS-associated cutaneous cylindromas.
• To determine if MYB activation is a common mechanism in cylindroma pathogenesis.
• To explore MYB as a potential therapeutic target.

Main Methods:

• Histopathological analysis of cylindroma and cylindrocarcinoma samples.
• Detection of MYB-NFIB fusion transcripts using molecular techniques.
• RNA interference to assess the effect of MYB inhibition on cell proliferation.

Main Results:

• BSS-associated cylindromas with CYLD defects lack MYB-NFIB fusion but show wild-type MYB activation.
• Sporadic cylindromas also exhibit MYB activation, either via MYB-NFIB fusion or wild-type MYB.
• Inhibition of MYB significantly reduced proliferation in BSS-derived cylindroma cells.

Conclusions:

• MYB activation is a key event in both sporadic and hereditary cutaneous cylindromas.
• Wild-type MYB plays a crucial role in cylindroma cell proliferation.
• Targeting MYB represents a promising therapeutic avenue for cylindroma treatment.