Identification of the familial cylindromatosis tumour-suppressor gene

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) ha s previously been localized to chromosome 16q and has the genetic attribute s of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and so matic mutations in 1 sporadic and 5 familial cylindromas. All mutations pre dict truncation or absence of the encoded protein. CYLD encodes three cytos keletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are f ound in proteins that coordinate the attachment of organelles to microtubul es. CYLD also has sequence homology to the catalytic domain of ubiquitin ca rboxy-terminal hydrolases (UCH).