title: A case of Brooke-Spiegler syndrome with a novel mutation in the CYLD gene in a patient with aggressive non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Brooke-Spiegler syndrome (BSS, familial cylindromatosis) is a rare hereditary disease characterized by multiple tumors of the skin appendages predominantly located in the head and neck region, such as cylindromas, trichoepitheliomas, or spiradenomas. It is caused by an autosomal dominant mutation in the CYLD gene, mapped on chromosome 16q12-13. Association with secondary malignant neoplasms has been reported. Until now 51 different mutations in 73 families have been reported; 41 % of them constitute frameshift mutations, resulting in an interruption of the expression of the gene product CYLD. CYLD is a deubiquitinating enzyme and plays an important role in (NF)-κB pathway signaling, a central pathway for apoptosis regulation. Mutation-induced loss of function leads to constitutive activation of NF-κB.
  
  
  METHODS
  Here, we report the case of a 48-year-old female patient diagnosed with an abdominal aggressive non-Hodgkin's lymphoma. The patient presented with multiple cylindromas of the capillitium. The patient's mother also has a mild form of late-onset cylindromas. Due to the typical clinical features indicating BSS, genotyping from peripheral blood was performed. A c.2465insAACA mutation in exon 17 of the CYLD gene, leading to a frameshift, was detected in the patient and in the patient's mother.
  
  
  CONCLUSIONS
  This is the first description of this hereditary mutation in exon 17 of the CYLD gene. There have been several reports on patients with CYLD mutations and different types of malignancies. However, a coincidence with aggressive non-Hodgkin's lymphoma has not been reported yet.
authors.affiliation: Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany. friederike.hunstig@med.uni-jena.de.
authors.forename: F
authors.initials: F
authors.lastname: Hunstig
authors.affiliation: Zentrum für Humangenetik, Universitätsklinikum Jena, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Nieten
authors.affiliation: Institut für angewandte Humangenetik und Onkogenetik, Bad Steben, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Froster
authors.affiliation: Institut für Pathologie, SRH-Waldklinikum Gera, Gera, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Boltze
authors.affiliation: Klinik für Hautkrankheiten, Universitätsklinikum Jena, Jena, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schliemann
authors.affiliation: Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: P
authors.initials: P
authors.lastname: La Rosée
mesh_terms: D000008:Abdominal Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D019008:Drug Resistance, Neoplasm; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*; D008875:Middle Aged; D009035:Mothers; D009102:Multiple Organ Failure; D009386:Neoplastic Syndromes, Hereditary / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D009679:Nuclear Family; D049268:Positron-Emission Tomography; D018714:Radiotherapy, Adjuvant; D012878:Skin Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
keywords: Brooke–Spiegler syndrome; CYLD gene; Case report; Non-Hodgkin’s lymphoma; Novel mutation