Phenotype variability in tumor disorders of the skin appendages associated with mutations in the CYLD gene

Abstract

Mutations in the tumor suppressor gene CYLD underlie phenotypically heterogeneous hereditary tumor disorders of the skin appendages. These diseases are inherited autosomal dominantly and include Brooke-Spiegler syndrome (BSS; OMIM 605041), familial cylindromatosis (FC; OMIM 132700) and multiple familial trichoepithelioma (MFT; OMIM 601606). Clinically, cylindromas, trichoepitheliomas and spiradenomas can be found in affected individuals. We sought to elucidate the molecular genetic basis in individuals with newly diagnosed cylindromas, trichoepitheliomas and/or spiradenomas. Mutation analysis using polymerase chain reaction (PCR)-based techniques was performed in seven German patients and one Turkish patient. We detected two missense, two nonsense, two deletions and two duplication mutations in the CYLD gene, of which seven have not yet been reported. No genotype-phenotype correlation was detected amongst the patients. Our data provide additional information on the clinical and molecular genetic heterogeneity of disorders associated with CYLD mutations.

CENPV Is a CYLD-Interacting Molecule Regulating Ciliary Acetylated α-Tubulin

“…The cylindromatosis gene CYLD was originally identified as a tumor suppressor related to Brooke-Spiegler syndrome (OMIM 605041) (Bignell et al, 2000;Ke et al, 2013), a familial disease associated with different skin appendage neoplasms such as cylindromas (CYLs), trichoepitheliomas (TEs), and spiradenomas (Dubois et al, 2017b). Different CYLD mutations with a variable phenotype have been reported (Andersson et al, 2019;Dubois et al, 2017a;Farkas et al, 2016;Parren et al, 2018). In rare cases, tumors in the parotids, salivary glands, breasts, or lungs are found (Tantcheva-Poó r et al, 2016).…”

Metastatic cylindrocarcinoma in Brooke‐Spiegler Syndrome – Report of a case and review of the literature

“…Genetic analysis showed a mutation in the CYLD gene, c.2241G>C; p.Glu747Asp. This variant has not been described before [7] and is found at the end of exon 16. A mutation from glutamate to glycine, Glu747Gly, has already been reported to cause BRSS [8].…”

“…Multiple cylindromas are associated with BRSS, whereas solitary cylindromas typically occur without association to BRSS [7]. According to Kazakov, the malignant component of spiradenocarcinomas, spirandenocylind romacarcinomas and cylindrocarcinomas can be classified by four different patterns: the salivary gland type basal cell adenocarcinoma-like pattern (low-grade), the salivary gland type basal cell adenocarcinoma-like pattern (high-grade), the invasive adenocarcinoma, with an otherwise unspecified pattern and the sarcomatoid carcinoma pattern [1].…”

Metastasierendes Zylindrokarzinom beim Brooke‐Spiegler‐Syndrom ‐ Fallbericht und Literaturübersicht

“…Die genetische Analyse ergab eine Mutation im CYLD-Gen, c.2241G>C; p.Glu747Asp. Diese bisher noch nicht beschriebene Variante [7] befindet sich am Ende von Exon 16. Es wurde bereits berichtet, dass eine Mutation von Glutamat zu Glycin, Glu747Gly, BRSS verursacht [8].…”