Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Sophie Sneddon; Justine S Leon; Ian M Dick; Gemma Cadby; Nola Olsen; Fraser Brims; Richard J N Allcock; Eric K Moses; Phillip E Melton; Nicholas de Klerk; A W Bill Musk; Bruce W S Robinson; Jenette Creaney

doi:10.1016/j.gene.2015.03.031

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma

Gene. 2015 May 25;563(1):103-5. doi: 10.1016/j.gene.2015.03.031. Epub 2015 Mar 18.

Authors

Affiliations

¹ National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia.
² 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.
³ School of Population Health, University of Western Australia, Nedlands, Western Australia 6009, Australia.
⁴ 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.
⁵ School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6009, Australia.
⁶ Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, Western Australia 6009, Australia.
⁷ Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia 6009, Australia.
⁸ 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.
⁹ 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.
¹⁰ 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.

PMID: 25796603
DOI: 10.1016/j.gene.2015.03.031

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.

Keywords: BAP1; Cancer syndrome; Mesothelioma; Mutation; Sporadic; Targeted sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Asbestos / adverse effects
Australia
Female
Genetic Predisposition to Disease
Germ-Line Mutation*
Humans
Lung Neoplasms / chemically induced
Lung Neoplasms / genetics*
Male
Mesothelioma / chemically induced
Mesothelioma / genetics*
Mesothelioma, Malignant
Middle Aged
Tumor Suppressor Proteins / genetics*
Ubiquitin Thiolesterase / genetics*

Substances

BAP1 protein, human
Tumor Suppressor Proteins
Asbestos
Ubiquitin Thiolesterase