title: Brooke-Spiegler syndrome tumor spectrum beyond the skin: a patient carrying germline R936X CYLD mutation and a somatic CYLD mutation in Brenner tumor.
abstract: Brooke-Spiegler syndrome is a hereditary disorder characterized by a predisposition to the development of skin appendage neoplasms and the major and minor salivary glands neoplasms. The role of the CYLD mutation in visceral neoplasms is still unclear, except for the parathyroid tumor. We report the case of a 46-year-old patient with multiple cylindromas and trichoepitheliomas, a Brenner tumor of the ovary and a negative family history for Brooke-Spiegler phenotype. Genetic analysis revealed R936X germline mutation in the proband, but not in the patient's relatives. The same somatic mutation was found in the Brenner tumor, together with a novel missense CYLD mutation (D889N), which has never been reported in the literature. A founder effect for R936X has been hypothesized due to its high prevalence; surprisingly, in our case, this mutation seems to be recognized as a de novo mutation. Future studies involving a greater number of cases, through the clinical analysis of the familial tumor spectrum and the associated molecular pathways, are necessary to understand possible genotype/phenotype correlations and the underlying molecular mechanisms.
authors.affiliation: Department of Diagnostic & Clinical Medicine & Public Health, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Cristel
authors.initials: C
authors.lastname: Ruini
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.forename: Francesca
authors.initials: F
authors.lastname: Farnetani
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Alexander Michal
authors.initials: AM
authors.lastname: Witkowski
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarrà
authors.forename: Aldo
authors.initials: A
authors.lastname: Tomasi
authors.forename: Pietro
authors.initials: P
authors.lastname: Loschi
authors.forename: Sabina
authors.initials: S
authors.lastname: Nasti
mesh_terms: D001483:Base Sequence; D001948:Brenner Tumor / Q000175:diagnosis* / Q000235:genetics; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis* / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD