title: Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32.
abstract: Genome-wide array-based comparative genomic hybridization analysis of malignant pleural mesotheliomas (MPM) was carried out to identify regions that display DNA copy number alterations. Seventeen primary tumors and nine cell lines derived from 22 individuals were studied, some of them originating from the same patients. Regions of genomic aberrations observed in >20% of individuals were 1q, 5p, 7p, 8q24 and 20p with gains, and 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 4q34-qter, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q with losses. Two regions at 1p32.1 and 11q22 showed a high copy gain. The 1p32.1 region contained a protooncogene, JUN, and we further demonstrated overexpression of JUN with real-time polymerase chain reaction analysis. As MPM cell lines did not overexpress JUN, our findings suggested that induction of JUN expression was involved in the development of MPM cells in vivo, which also might result in gene amplification in a subset of MPM. Meanwhile, the most frequent alteration was the 9p21.3 deletion, which includes the p16(INK4a)/p14(ARF) locus. With polymerase chain reaction analysis, we determined the extent of the homozygous deletion regions of the p16(INK4a)/p14(ARF) locus in MPM cell lines, which indicated that the deletion regions varied among cell lines. Our results with array comparative genomic hybridization analysis provide new insights into the genetic background of MPM, and also give some clues to develop a new molecular target therapy for MPM.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Sivasundaram
authors.initials: S
authors.lastname: Karnan
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukui
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tagawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ueda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D016758:Genes, jun; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers