title: Association between Birt Hogg Dube syndrome and cancer predisposition.
abstract: The Birt Hogg Dubé syndrome (BHD) is a rare autosomal dominant genodermatosis predisposing patients to developing fibrofolliculoma, trichodiscoma and acrochordon. The syndrome is caused by germline mutations in the folliculin (FLCN) gene, encoding the folliculin tumor-suppressor protein. Numerous mutations have been described in the FLCN gene, the most frequent occurring within a C8 tract of exon 11. This hypermutability is probably due to a slippage in DNA polymerase during replication, resulting in gains/losses of repeat units, causing cancer predisposition. The main phenotypic manifestations related to this disease are lung cysts, leading to pneumothorax, and a 7-fold increased risk for renal neoplasia, although other neoplastic manifestations have been described in BHD-affected individuals. Of particular interest is the often reported genotype/phenotype correlation between FLCN mutations and risk of colon or breast cancer. This paper describes our current knowledge on the association between BHD and cancer predisposition and briefly summarizes our experience in this field.
authors.affiliation: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele, Via della Pisana 235, 00163, Rome, Italy. raffaele.palmirotta@sanraffaele.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.forename: Giorgia
authors.initials: G
authors.lastname: Ludovici
authors.forename: Pietro
authors.initials: P
authors.lastname: Donati
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavaliere
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: DE Marchis
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
mesh_terms: D003560:Cysts / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins