title: Germline mutations causing familial lung cancer.
abstract: Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic 'candidate' mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tomoshige
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oikawa
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamasaki
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hiroyuki
authors.identifier: http://orcid.org/0000-0001-5050-2509
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Internal Medicine, The Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Nagasaki, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Internal Medicine, The Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Nagasaki, Japan.
authors.forename: Kiyoyasu
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
mesh_terms: D000328:Adult; D000368:Aged; D059472:Exome; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D009363:Neoplasm Proteins