A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib
Language English Country Germany Media print-electronic
Document type Case Reports, Journal Article
PubMed
29934657
DOI
10.1007/s00428-018-2397-y
PII: 10.1007/s00428-018-2397-y
Knihovny.cz E-resources
- Keywords
- Brooke syndrome, CYLD, Hedgehog pathway, Trichoepithelioma, Vismodegib,
- MeSH
- Anilides therapeutic use MeSH
- Neoplastic Syndromes, Hereditary drug therapy genetics metabolism pathology MeSH
- Heredity MeSH
- Deubiquitinating Enzyme CYLD genetics MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease MeSH
- Immunohistochemistry MeSH
- Middle Aged MeSH
- Humans MeSH
- Skin Neoplasms drug therapy genetics metabolism pathology MeSH
- Codon, Nonsense MeSH
- Tomography, X-Ray Computed MeSH
- Zinc Finger Protein GLI1 genetics metabolism MeSH
- Antineoplastic Agents therapeutic use MeSH
- Pyridines therapeutic use MeSH
- Pedigree MeSH
- Signal Transduction drug effects MeSH
- Up-Regulation MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- Anilides MeSH
- CYLD protein, human MeSH Browser
- Deubiquitinating Enzyme CYLD MeSH
- GLI1 protein, human MeSH Browser
- HhAntag691 MeSH Browser
- Codon, Nonsense MeSH
- Zinc Finger Protein GLI1 MeSH
- Antineoplastic Agents MeSH
- Pyridines MeSH
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.
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