Familial cylindromatosis mimicking tuberous sclerosis complex and confirmation of the cylindromatosis locus, CYLD1, in a large family.

Verhoef, Senno; Schrander-Stumpel, C. T. R. M.; Vuzevski, V. D.; Tempelaars, A.; Jansen, Laura A.; Malfeyt, G. A. M.; Ceelen, T. L.; Lindhout, Dick; Halley, Dicky; Ouweland, Ans M.W. van den

doi:10.1136/jmg.35.10.841

Cited by 18 publications

(14 citation statements)

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“…D16S770, which is non-recombinant here, is just 0.67 cM distal to D16S416, the distal recombinant marker in the other family reported by Biggs et al (1995). Verhoef et al (1998) did not report recombinant markers on 16q. Thus, the non-recombinant interval in this family is approximantly 15 cM, with no recombination that narrows the published CYLD1 6-cM interval (Biggs et al 1995).…”

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confidence: 72%

“…This suggested that CYLD1 is a tumor suppressor gene that follows the classic two-hit model (Knudson 1971). Verhoef et al (1998) reported a Dutch family also linked to CYLD1 and in which three tumors showed LOH at one non-recombinant marker (no further tumor analysis was performed). In addition, 16q LOH has been observed in sporadic HC tumors, suggesting that the same gene is involved in both familial and sporadic forms (Biggs et al 1996).…”

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confidence: 95%

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A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16

et al. 1999

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Hereditary cylindromatosis (HC; MIM 132700) is an autosomal dominant condition characterized by benign skin appendage tumors most commonly on the scalp and face. Previously, the HC gene (CYLD1) was linked to chromosome 16q12-13, and tumors showed loss of heterozygosity (LOH), suggesting that CYLD1 is a tumor suppressor gene. Here we report a new multi-generation cylindromatosis family whose condition maps to that region, with 7/13 tumors showing LOH on 16q.

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confidence: 72%

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confidence: 95%

A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16

et al. 1999

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“…Furthermore, TEs and cylindromas often coexist in patients with the tumor predisposition syndrome hereditary multiple epithelioma (MIM 132700) (37,38). TE and BCC occur in the multiple familial TE syndrome (MIM 60͞606), and trichoblastoma and BCC often develop within a congenital malformation called sebaceous nevus, in which deletions in the PTCH1 gene region were recently reported (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1

Nilsson

Undén²,

Krause³

et al. 2000

Proceedings of the National Academy of Sciences

241

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Basal cell carcinoma is the most prevalent cancer in the western world, showing a rapid increase in incidence. Activation of the Sonic hedgehog͞Patched (PTCH) signaling pathway because of PTCH1 inactivation is a key event in sporadic and familial basal cell carcinoma development in humans and is associated with transcriptional activation of specific target genes, including PTCH1 itself. These changes are analogous to the situation in Drosophila where hedgehog activates the zinc-finger transcription factor Cubitus interruptus, leading to increased transcription of target genes. In the present study, we show that mice ectopically expressing the human Cubitus interruptus homolog GLI-1 in the skin develop tumors closely resembling human BCCs as well as other hair follicle-derived neoplasias, such as trichoepitheliomas, cylindromas, and trichoblastomas. Furthermore, examination of the tumors revealed wild-type p53 and Ha ras genes. These findings firmly establish that increased GLI-1 expression is central and probably sufficient for tumor development and suggest that GLI-1-induced tumor development does not depend on additional p53 or Ha ras mutations.G enetic studies on patients with nevoid basal cell carcinoma syndrome (NBCCS), which predisposes affected individuals to the development of multiple basal cell carcinomas (BCCs), have led to the identification of inactivating mutations in the human homolog of the Drosophila gene patched (PTCH1) as the defect underlying this syndrome (1, 2). In addition, a number of surveys have provided evidence that mutations in the PTCH1 locus is a significant cause of sporadic BCCs as well as other hair follicle-derived neoplasias such as trichoepitheliomas (TEs) (3-5). The other common genetic alteration in BCCs is a mutation in the tumor-suppressor gene p53 (6).In biochemical assays, Ptch1 has been shown to bind the ligand Sonic hedgehog (Shh) (7,8). Ptch1 is a transmembrane protein that together with Smoothened (Smoh), a seven-transmembrane protein, forms a receptor complex for Shh (9, 10). Ligand binding results in derepression of signaling from Smoh and subsequently to activation of the transcription factor Gli, the mammalian homolog to Drosophila Cubitus interruptus (Ci). Three Ci homologs have been identified in mammals, Gli-1, Gli-2, and Gli-3, which share a highly conserved zinc-finger domain with Ci and are believed to function as the most downstream components in the vertebrate Sonic hedgehogPatched signaling pathway (11,12). The precise roles played by the three Gli genes have not yet been fully defined. GLI-1 was originally isolated as an amplified gene in a glioma and can transform primary rat cells in cooperation with adenovirus E1A (13). Several lines of evidence suggest a role for Gli-1 in mediating the Shh signal: first, Gli-1 is expressed in cells that are responsive to Shh (14,15). Second, elevated Gli-1 expression is observed in Shh-treated cells, and third, ectopic expression of Gli-1 in the dorsal midbrain and hindbrain mimics the effects of ectopically expres...

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“…Subsequently, two additional families have been published, both of which exhibit strong evidence of linkage to this locus (Verhoef et al 1998;Thomson et al 1999). Analysis of tumours from the original two families has shown that more than 70% exhibit loss of heterozygosity (LOH) in the vicinity of CYLD and, in all cases, the allele lost is the wild-type allele inherited from the non-mutation-carrying parent (Biggs et al 1995).…”

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confidence: 97%

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13

et al. 2000

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Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations.

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Familial cylindromatosis mimicking tuberous sclerosis complex and confirmation of the cylindromatosis locus, CYLD1, in a large family.

Abstract: A large Dutch family had been known for many years to be affected with skin tumours labelled as adenoma sebaceum, which were inherited in an autosomal dominant fashion.

Cited by 18 publications

References 7 publications

A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16

A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16

Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1

Linkage and LOH studies in 19 cylindromatosis families show no evidence of genetic heterogeneity and refine the CYLD locus on chromosome 16q12-q13

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