title: Integrated high-resolution array CGH and SKY analysis of homozygous deletions and other genomic alterations present in malignant mesothelioma cell lines.
abstract: High-resolution oligonucleotide array comparative genomic hybridization (aCGH) and spectral karyotyping (SKY) were applied to a panel of malignant mesothelioma (MMt) cell lines. SKY has not been applied to MMt before, and complete karyotypes are reported based on the integration of SKY and aCGH results. A whole genome search for homozygous deletions (HDs) produced the largest set of recurrent and non-recurrent HDs for MMt (52 recurrent HDs in 10 genomic regions; 36 non-recurrent HDs). For the first time, LINGO2, RBFOX1/A2BP1, RPL29, DUSP7, and CCSER1/FAM190A were found to be homozygously deleted in MMt, and some of these genes could be new tumor suppressor genes for MMt. Integration of SKY and aCGH data allowed reconstruction of chromosomal rearrangements that led to the formation of HDs. Our data imply that only with acquisition of structural and/or numerical karyotypic instability can MMt cells attain a complete loss of tumor suppressor genes located in 9p21.3, which is the most frequently homozygously deleted region. Tetraploidization is a late event in the karyotypic progression of MMt cells, after HDs in the 9p21.3 region have already been acquired.
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Geula
authors.initials: G
authors.lastname: Klorin
authors.forename: Ester
authors.initials: E
authors.lastname: Rozenblum
authors.forename: Oleg
authors.initials: O
authors.lastname: Glebov
authors.forename: Robert L
authors.initials: RL
authors.lastname: Walker
authors.forename: Yoonsoo
authors.initials: Y
authors.lastname: Park
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Ilan R
authors.initials: IR
authors.lastname: Kirsch
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Kaye
authors.forename: Anna V
authors.initials: AV
authors.lastname: Roschke
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D055028:Comparative Genomic Hybridization; D017353:Gene Deletion; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008654:Mesothelioma / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D032681:Spectral Karyotyping
keywords: Malignant mesothelioma; homozygous deletions; oligonucleotide array CGH; spectral karyotyping; tumor suppressors