Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

2–18% of ductal carcinoma-No Special Type (NST) are reported to express basal cell keratin 14 and such tumours may have a different metastatic pattern and prognosis. We performed immunohistochemistry for cytokeratins 19 (luminal) and 14 (basal) on 92 ductal carcinoma-NST. Those tumours showing CK14 expression were further characterized by immunohistochemistry for myoepithelial cell phenotype and analysed by comparative genomic hybridization. The 7 cases of ductal carcinoma-NST exhibiting a basal cell phenotype were all grade III tumours and showed a molecular cytogenetic profile similar to more conventional myoepithelial cell carcinomas. Therefore it appears that grade III invasive ductal carcinomas contain a subset of tumours with specific morphological and cytogenetic characteristics, and probably prognosis for the patient. © 2001 Cancer Research Campaign http://www.bjcancer.com

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The relationship of apocrine metaplasia to invasive breast cancer is controversial. Different authors have reported that apocrine differentiation in proliferative lesions may be a risk factor, a precursor lesion, or have no association with malignancy. The aim of this study was to compare the genetic alterations in benign apocrine hyperplasia with apocrine ductal carcinoma in situ (DCIS) and invasive apocrine carcinomas of the breast using comparative genomic hybridization. The mean number of alterations in apocrine hyperplasia was 4.1 (n = 10) compared to 10.2 in apocrine DCIS (n = 10) and 14.8 (n = 4) in invasive carcinoma. The most common alterations in apocrine hyperplasia were gains of 2q, 13q, and 1p and losses of 1p, 17q, 22q, 2p, 10q, and 16q. Apocrine DCIS and invasive carcinomas showed gains of 1q, 2q, 1p, and losses of 1p, 22q, 17q, 12q, and 16q as their most common DNA copy number changes. Apocrine hyperplasia is considered to be a benign lesion and its relationship to invasive carcinoma remains unclear. Our data suggest that some apocrine hyperplasias may be clonal proliferations. The mean number of alterations are lower in apocrine hyperplasia, however the changes show considerable overlap with those identified in in situ and invasive apocrine carcinoma. These alterations are also commonly seen in nonapocrine breast cancer. The data are consistent with apocrine hyperplasia as a putative nonobligate precursor of apocrine carcinoma.