title: Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level.
abstract: Malignant mesothelioma (MM) is an asbestos-related malignancy arising from surface serosal cells of pleural and peritoneal cavities. Somatic mutations of BRCA1 associated protein-1 (BAP1) gene were recently found in MM as well as in uveal melanoma and kidney cancer among the Caucasian and Japanese people. However, frequency of mutations varies among the reported studies, which might be due to presence of undetected gross rearrangements of BAP1 gene that might escape detection by sequencing strategy. We investigated the presence and frequency of gross genomic rearrangements in the BAP1 gene by multiplex ligation-dependent probe amplification (MLPA) in 17 Japanese cases of MM tumors. We found five tumors with partial deletion of BAP1 gene; each tumors displayed partial deletion of exons 1-4 (MM39), exons 1-5 (MM48), exons 11-17 (MM57), exons 1-15 (MM19) and exons 1-16 (MM21). Two tumors (MM34, MM14) had biallelic deletion and four tumors (MM29, MM35, MM45 and MM56) had monoallelic deletion of entire BAP1 gene. Therefore, MLPA analysis revealed large gene rearrangements of BAP1 gene in 65% of MM (11/17). Unusually high frequency of large deletions indicates that the 3p21 chromosomal region surrounding BAP1 gene is structurally unstable. MLPA was useful in characterizing both monoallelic and biallelic deletion of BAP1 gene precisely at exon level.
authors.affiliation: Department of Genetics, Hyogo College of Medicine, Hyogo, Japan.|Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.affiliation: Department of Genetics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Clinical Genetics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Sato
authors.affiliation: Department of Molecular Pathology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Ayuko
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Molecular Pathology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.affiliation: Department of General Thoracic Surgery, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Genetics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hashimoto-Tamaoki
mesh_terms: D044466:Asian People; D001483:Base Sequence; D043171:Chromosomal Instability; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008654:Mesothelioma / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase