● Enzyme Number (IUBMB): EC 126.96.36.199, EC 188.8.131.52
Cylindromatosis (turban tumor syndrome)
956 amino acids; about 107 kDa
This gene encodes a cytoplasmic protein that functions as a deubiquitinating enzyme. It is a negative regulator of various signaling pathways, including TRAF2 and NF-kappa-B signaling pathways.
Mutations in CYLD have been associated with familial cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome.
Familial cylindromatosis is an autosomal dominant and highly tumor type-specific disorder. The tumors (known as cylindromas because of their characteristic microscopic architecture) are believed to arise from or recapitulate the appearance of the eccrine or apocrine cells of the skin that secrete sweat and scent respectively. Cylindromas arise predominantly in hairy parts of the body with approximately 90% on the head and neck. The development of a confluent mass which may ulcerate or become infected has led to the designation 'turban tumor syndrome'. The skin tumors show differentiation in the direction of hair structures, hence the synonym trichoepithelioma.
Multiple familial trichoepithelioma (MFT1). MFT1 is an autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma.
Brooke-Spiegler syndrome (BRSS). BRSS is an autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life.
Among tumors, CYLD alterations, mostly substitutions or insertions, have been observed only in skin tumors. No specific mutation hot spot has been described to date.
References (open access):
CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes. Sun SC. Cell Death Differ. 2010 Jan;17(1):25-34.
Identification of a large rearrangement in CYLD as a cause of familial cylindromatosis. van den Ouweland AM, Elfferich P, Lamping R, van de Graaf R, van Veghel-Plandsoen MM, Franken SM, Houweling AC. Fam Cancer. 2011 Mar;10(1):127-32.