Multiple familial trichoepitheliomas (MFT) is an autosomal dominantly inherited disease characterized by multiple skin appendage tumors. We describe a patient showing a continuous spectrum of follicular differentiated neoplasms including classical trichoepitheliomas but also infiltrative growing and finally metastasizing malignant follicular differentiated tumors. Germline mutation analysis revealed a nonsense mutation in the cylindromatosis (CYLD) gene. Gene expression analysis by real-time PCR of tumor tissue showed overexpression of glioma-associated oncogene Gli1 mRNA. Treatment with the Hedgehog pathway inhibitor vismodegib resulted in a significant regression of the highly differentiated trichoepitheliomas. Gli upregulation is indicative of an active Hedgehog signaling pathway. We hypothesize that its upregulation is indirectly caused by CYLD mutation which promotes tumor development. Vismodegib treatment could thus provide a new treatment option for patients with this debilitating disorder.

• Klíčová slova
• Brooke syndrome, CYLD, Hedgehog pathway, Trichoepithelioma, Vismodegib,
• MeSH
• anilidy terapeutické užití   MeSH
• dědičné nádorové syndromy farmakoterapie   genetika   metabolismus   patologie   MeSH
• dědičnost MeSH
• deubikvitinizační enzym CYLD genetika   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory kůže farmakoterapie   genetika   metabolismus   patologie   MeSH
• nesmyslný kodon MeSH
• počítačová rentgenová tomografie MeSH
• protein Gli1 genetika   metabolismus   MeSH
• protinádorové látky terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• rodokmen MeSH
• signální transdukce účinky léků   MeSH
• upregulace MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• anilidy MeSH
• CYLD protein, human MeSH Prohlížeč
• deubikvitinizační enzym CYLD MeSH
• GLI1 protein, human MeSH Prohlížeč
• HhAntag691 MeSH Prohlížeč
• nesmyslný kodon MeSH
• protein Gli1 MeSH
• protinádorové látky MeSH
• pyridiny MeSH

Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms most commonly spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. Multiple familial trichoepithelioma (MFT) is a phenotypic variant of the disease characterized by the development of numerous trichoepitheliomas (cribriform trichoblastoma) only. Malignant tumors arise in association with preexisting benign cutaneous neoplasms in about 5-10% of the patients . Apart from the skin, major and minor salivary glands have been rarely involved in BSS patients. Extremely rare is the occurrence of breast tumors (cylindroma). The gene implicated in the pathogenesis of the disease is the CYLD gene, a tumor suppressor gene located on chromosome 16q12-q13. Germline CYLD mutations are detected in about 80-85% of patients with the classical BSS phenotype and in about 40-50% of the individuals with the MFT phenotype using a PCR based approach with analysis of exonic sequences and exon-intron junctions of the CYLD gene. There appears to be no genotype-phenotype correlations with respect to the severity of the disease, the possibility of malignant transformation, and development of extracutaneous lesions.

• Klíčová slova
• Brooke-Spiegler syndrome, CYLD gene, Cylindroma, Spiradenoma, Trichoepithelioma,
• MeSH
• dědičné nádorové syndromy * genetika   patologie   MeSH
• deubikvitinizační enzym CYLD MeSH
• fenotyp MeSH
• genotyp MeSH
• lidé MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory kůže * genetika   patologie   MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• CYLD protein, human MeSH Prohlížeč
• deubikvitinizační enzym CYLD MeSH
• nádorové supresorové proteiny MeSH