title: Locus-specific multifluor FISH analysis allows physical characterization of complex chromosome abnormalities in neoplasia.
abstract: Novel techniques in molecular cytogenetics have radically improved the ability to characterize genetic changes in neoplastic cells. In parallel, a rapid development in high-throughput genomics has resulted in detailed physical maps of the human genome. Combining these two fields, we have developed a method for the simultaneous visualization of several physically defined segments along a chromosome. Seven YAC clones and one subtelomeric cosmid clone from chromosome 12 were labeled with unique combinations of four fluors and hybridized to metaphase chromosomes from neoplastic cells. In a uterine leiomyoma and a myxoid liposarcoma with translocations 12;14 and 12;16, the breakpoints in chromosome 12 could be localized to the HMGIC and CHOP regions, respectively. In the other tumors, more complex aberrations were visualized, including two inversions in 12q with a common breakpoint between MDM2 and D12S332 in a pleomorphic adenoma, amplification of MDM2 and CDK4 in ring chromosomes from a malignant fibrous histiocytoma, and amplification of KRAS2 together with other unbalanced rearrangements in two pancreatic adenocarcinomas. Combinatorially labeled single-copy probes may thus simultaneously provide physical localization of breakpoints and an overview of complex structural rearrangements. Genes Chromosomes Cancer 28:347-352, 2000.
authors.affiliation: Department of Clinical Genetics, University Hospital, Lund, Sweden. david.gisselsson@klingen.lu.se
authors.forename: D
authors.initials: D
authors.lastname: Gisselsson
authors.forename: N
authors.initials: N
authors.lastname: Mandahl
authors.forename: E
authors.initials: E
authors.lastname: Pålsson
authors.forename: L
authors.initials: L
authors.lastname: Gorunova
authors.forename: M
authors.initials: M
authors.lastname: Höglund
mesh_terms: D002869:Chromosome Aberrations / Q000175:diagnosis / Q000235:genetics*; D025063:Chromosome Disorders; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003116:Color; D005260:Female; D005456:Fluorescent Dyes; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020161:Physical Chromosome Mapping / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D005456:Fluorescent Dyes; D005819:Genetic Markers