title: Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.
abstract: Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Sophie
authors: S
authors: Sneddon
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Justine S
authors: JS
authors: Leon
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Ian M
authors: IM
authors: Dick
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia; Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Gemma
authors: G
authors: Cadby
authors: School of Population Health, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Nola
authors: N
authors: Olsen
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia; Lung Institute of Western Australia, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Fraser
authors: F
authors: Brims
authors: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Richard J N
authors: RJ
authors: Allcock
authors: Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Eric K
authors: EK
authors: Moses
authors: Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Phillip E
authors: PE
authors: Melton
authors: Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: Nicholas
authors: N
authors: de Klerk
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia; School of Population Health, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors: A W Bill
authors: AW
authors: Musk
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
authors: Bruce W S
authors: BW
authors: Robinson
authors: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia. Electronic address: jenette.creaney@uwa.edu.au.
authors: Jenette
authors: J
authors: Creaney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001194:Asbestos / Q000009:adverse effects; D001315:Australia; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D001194:Asbestos; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Cancer syndrome; Mesothelioma; Mutation; Sporadic; Targeted sequencing