title: Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis?
abstract: Renal cell cancer (RCC) represents 2-3% of all cancers and is the most lethal of the urologic malignancies, in a minority of cases caused by a genetic predisposition. Birt-Hogg-Dubé syndrome (BHD) is one of the hereditary renal cancer syndromes. As the histological subtype and clinical presentation in BHD are highly variable, this syndrome is easily missed. Lung cysts--mainly under the main carina--are reported to be present in over 90% of all BHD patients and might be an important clue in differentiating between sporadic RCC and BHD associated RCC. We conducted a retrospective study among patients diagnosed with sporadic RCC, wherein we retrospectively scored for the presence of lung cysts on thoracic CT. We performed FLCN mutation analysis in 8 RCC patients with at least one lung cysts under the carina. No mutations were identified. We compared the radiological findings in the FLCN negative patients to those in 4 known BHD patients and found multiple basal lung cysts were present significantly more frequent in FLCN mutation carriers and may be an indication for BHD syndrome in apparent sporadic RCC patients.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. p.johannesma@vumc.nl.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Johannesma
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Houweling
authors.affiliation: Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Menko
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: van de Beek
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rinze
authors.initials: R
authors.lastname: Reinhard
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Johan J P
authors.initials: JJ
authors.lastname: Gille
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: JanHein T M
authors.initials: JT
authors.lastname: van Waesberghe
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Starink
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, Clatterbridge Cancer Centre, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, UK.
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.affiliation: Department of Urology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R Jeroen A
authors.initials: RJ
authors.lastname: van Moorselaar
mesh_terms: D058249:Birt-Hogg-Dube Syndrome / Q000209:etiology* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D003560:Cysts / Q000000981:diagnostic imaging / Q000209:etiology*; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: BHD; Birt–Hogg–Dubé syndrome; Folliculin; Pneumothorax; RCC; Renal cell cancer