RESUMO
AIM: The gene for familial cylindromatosis (CYLD) has been localised to chromosome 16q, and has recently been cloned. Loss of heterozygosity (LOH) at 16q has also been demonstrated in sporadic cylindromas. The aim of this study was to investigate whether CYLD plays a role in the development of other skin appendage tumours. METHODS: A total of 55 cases of skin adnexal tumours, comprising 12 different types, and a control group of 14 squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) were studied. Three microsatellites (D16S407 (16p), D16S304 (16q), and D16S308 (16q)) were analysed for LOH after microdissection from paraffin wax embedded sections using laser capture microdissection. RESULTS: In keeping with previous data, a proportion of cylindromas exhibited LOH at markers on 16q, but not at 16p. The skin adnexal tumours showing a similar pattern included apocrine hydrocystomas, eccrine spiradenomas, and sebaceous adenoma. One case of syringoma showed LOH at 16q, and a further case at 16p, but not 16q. One case of eccrine hydrocystoma showed loss at 16p, but not 16q. The remaining tumours were either negative or non-informative. All tumours in the control group were either negative or non-informative, except for a single case of BCC showing LOH at 16q. CONCLUSION: CYLD may be involved in the development of skin adnexal tumours other than cylindromas.
Assuntos
Carcinoma Adenoide Cístico/genética , Cromossomos Humanos Par 16 , Perda de Heterozigosidade , Proteínas/genética , Neoplasias das Glândulas Sudoríparas/genética , Proteínas Supressoras de Tumor , Adenoma/genética , Enzima Desubiquitinante CYLD , Genes Supressores de Tumor , HumanosRESUMO
The ky mouse mutant exhibits a primary degenerative myopathy preceding chronic thoraco-lumbar kyphoscoliosis. The histopathology of the ky mutant suggests that Ky protein activity is crucial for normal muscle growth and function as well as the maturation and stabilization of the neuromuscular junction. Muscle hypertrophy in response to increasing demand is deficient in the ky mutant, whereas adaptive fibre type shifts take place. The ky locus has previously been localized to a small region of mouse chromosome 9 and we have now identified the gene and the mutation underlying the kyphoscoliotic mouse. The ky transcript encodes a novel protein that is detected only in skeletal muscle and heart. The identification of the ky gene will allow detailed analysis of the impact of primary myopathy on idiopathic scoliosis in mice and man.
Assuntos
Músculos/metabolismo , Doenças Musculares/genética , Mutação , Escoliose/genética , Sequência de Aminoácidos , Animais , Northern Blotting , Clonagem Molecular , Modelos Animais de Doenças , Homozigoto , Hipertrofia , Imuno-Histoquímica , Camundongos , Microscopia Confocal , Microscopia de Vídeo , Modelos Genéticos , Dados de Sequência Molecular , Cadeias Pesadas de Miosina/química , Cadeias Pesadas de Miosina/genética , Junção Neuromuscular/anormalidades , Isoformas de Proteínas , Radiografia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escoliose/diagnóstico por imagem , Escoliose/metabolismo , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Transglutaminases/químicaRESUMO
The ky mouse mutant exhibits a degenerative muscle disease resulting in chronic deformation of the spinal column. Following a previous report describing the mapping of the ky locus to a small region of mouse chromosome 9 (Skynner et al., 1995, Genomics 25, 207-213), we have now undertaken a positional cloning approach to identify candidate genes for ky. A YAC/BAC contig encompassing the ky locus was constructed comprising 48 YAC clones and 48 newly generated STSs. The results from the combined physical and genetic analyses showed that only two overlapping BAC clones, which together do not exceed 260 kb, span the ky nonrecombinant region. A combination of gene hunting methods on the critical BACs has led to the identification of seven coding fragments, which have been tested for expression. The expression analysis and the position of the coding fragments on the contig suggest their grouping in at least four transcription units. One of these transcription units is expressed exclusively in skeletal muscle, making it a suitable candidate for this muscle defect in the ky mouse.
Assuntos
Cifose/genética , Mapeamento Físico do Cromossomo/métodos , Escoliose/genética , Sitios de Sequências Rotuladas , Animais , Cromossomos Artificiais de Levedura , Cromossomos Bacterianos , Mapeamento de Sequências Contíguas , Feminino , Masculino , Camundongos , Camundongos Mutantes , Recombinação GenéticaRESUMO
The ky mouse mutant, kyphoscoliosis, exhibits a degenerative muscle disease resulting in chronic deformation of the spinal column. Using an interspecific backcross segregating the ky mutation, we have mapped the ky locus to a small region of mouse chromosome 9. ky is nonrecombinant with the microsatellites D9Mit24 and D9Mit169 and lies in a conserved linkage group that encompasses human chromosome 3. s-Laminin (LAMS) and the gene for dystrophin-associated glycoprotein 1 (DAG1), which map to human chromosome 3, are both recombinant with ky, ruling them out as candidates.
