Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

Salhi, Aïcha; Bornholdt, Dorothea; Oeffner, Frank; Malik, Sajid; Heid, E; Happle, Rudolf; Grzeschik, Karl‐Heinz

doi:10.1158/0008-5472.can-04-0307

Cited by 70 publications

(55 citation statements)

References 41 publications

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“…Mutations of the CYLD gene have been reported among patients with Irish, Japanese, Spanish, German, Algerian, Turkish, Hungarian, Slovakian, Italian, Scandinavian, Taiwanese, Turkish, Canadian and African backgrounds [Bowen et al, 2005;Kacerovska et al, 2013;Saggar et al, 2008;Nagy et al, 2013;Nagy et al, 2012;Nasti et al, 2009;Salhi et al, 2004;Huang et al, 2009;Amaro et al, 2010]. However, the majority of the published mutations are reported for patients from the UK, USA and China [Bignell et al, 2000;Lv et al, 2008;Ying et al, 2012;Liang et al, 2008;Zheng et al, 2004;Chen et al, 2011;Wang et al, 2010;Zuo et al, 2007].…”

Section: Ethnic Variationmentioning

confidence: 99%

Phenotype–genotype correlations for clinical variants caused by CYLD mutations

Nagy

Farkas

Kemény

et al. 2015

European Journal of Medical Genetics

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Brooke-Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant condition characterized by skin appendageal neoplasms including cylindromas, trichoepitheliomas, and/or spiradenomas. In 1996, the gene locus for BSS was mapped to 16q12-13, and, in 2000, mutations in the cylindromatosis (CYLD) gene were determined to cause BSS, familial cylindromatosis (FC; OMIM 132700) and multiple familial trichoepithelioma type 1 (MFT1; OMIM 601606). The CYLD gene encodes an enzyme with deubiquitinase activity. To date, a total of 95 different diseases-causing mutations have been published for the CYLD gene. A summary of mutations identified in Hungarian patients and a review of previously published mutations are presented in this update. The majority of the sequence changes are frameshift (48%), nonsense (27%), missense (12%) and splice-site (11%) mutations; however, two in-frame deletions have also been reported Most mutations are located in exons 9-20. Analysis of the identified CYLD gene mutations and the observed BSS, FC and MFT1 clinical phenotypes of the patients revealed significant genotype-phenotype correlations. Elucidation of these genotype-phenotype correlations is critical for the diagnosis of these rare monogenic skin diseases. In addition, characterized correlations may promote the understanding of their mechanisms and may hopefully contribute to the development of future therapeutic modalities.

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Section: Ethnic Variationmentioning

confidence: 99%

Phenotype–genotype correlations for clinical variants caused by CYLD mutations

Nagy

Farkas

Kemény

et al. 2015

European Journal of Medical Genetics

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“…Nevertheless, some CYLD patients harbor trichoepitheliomas intermingled with cylindromas (Poblete-Gutie´rrez et al, 2002). Thus, whether there was a genetic relationship between the two diseases remained unclear; however, it is now known that some MFT patients also have mutations in CYLD (Salhi et al, 2004;Zhang et al, 2004;Zheng et al, 2004) (Figure 2), suggesting that cylindromatosis and MFT are two distinct manifestations of the same genetic defect. This discovery supports the view that precursor cells of the folliculo-sebaceous hair unit are indeed the cell types that become transformed upon CYLD dysfunction.…”

Section: Multiple Familial Trichoepitheliomamentioning

confidence: 99%

Mutations in the NF-κB signaling pathway: implications for human disease

2006

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“…(22)(23)(24)(25)(26) The lesions are primarily localised in the head, neck and face region. Solitary tumors typically occur sporadically and affect middle-aged and elderly individuals, while multiple tumors are seen in patients with inherited disorders.…”

Section: Cylindromatosis: Clinical and Genetic Featuresmentioning

confidence: 99%

Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control

Massoumi

Paus

2007

BioEssays

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Analysing cylindromatosis and the associated defects in the CYLD gene is providing novel insights into the molecular principles of epithelial growth control and carcinogenesis in, and beyond, the skin. In this review, we summarize the histopathology and histogenesis of cylindromas, and the available genetic information on patients with these skin appendage tumors. Focusing on recent data concerning the normal functions and signaling interactions of the CYLD gene product, we explain how CYLD interferes with TNF-alpha or TLR-mediated signaling as well as with JNK or NF-kappaB-dependent p65/50 signaling to limit inflammation. In addition, we delineate how CYLD interferes with activation of the proto-oncogene Bcl(3) and with cyclin D1 expression to limit tumorigenesis, and chart how tumor growth-promoting agents or UV light and inflammatory mediators can activate CYLD. We argue that these recent insights into CYLD function and cylindroma pathogenesis may lead to the development of novel molecular strategies for cancer prevention and treatment.

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Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

Cited by 70 publications

References 41 publications

Phenotype–genotype correlations for clinical variants caused by CYLD mutations

Phenotype–genotype correlations for clinical variants caused by CYLD mutations

Mutations in the NF-κB signaling pathway: implications for human disease

Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control

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