title: Analysis of chromosomal aberrations involving chromosome 1q31-->q53 in a DMBA-induced rat fibrosarcoma cell line: amplification and overexpression of Jak2.
abstract: In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome hybridization showed that there was amplification involving RNO1q31-->q53 in one of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived from it. To identify the amplified genes we physically mapped rat genes implicated in cancer and analyzed them for signs of amplification. The genes were selected based on their locations in comparative maps between rat and man. The rat proto-oncogenes Ccnd1, Fgf4, and Fgf3 (HSA11q13.3), were mapped to RNO1q43 by fluorescence in situ hybridization (FISH). The Ems1 gene was mapped by radiation hybrid (RH) mapping to the same rat chromosome region and shown to be situated centromeric to Ccnd1 and Fgf4. In addition, the proto-oncogenes Hras (HSA11p15.5) and Igf1r (HSA15q25-->q26) were mapped to RNO1q43 and RNO1q32 by FISH and Omp (HSA11q13.5) was assigned to RNO1q34. PCR probes for the above genes together with PCR probes for the previously mapped rat genes Bax (RNO1q31) and Jak2 (RNO1q51-->q53) were analyzed for signs of amplification by Southern blot hybridization. Low copy number increases of the Omp and Jak2 genes were detected in the LB31 cell culture. Dual color FISH analysis of tumor cells confirmed that chromosome regions containing Omp and Jak2 were amplified and were situated in long marker chromosomes showing an aberrant banding pattern. The configuration of the signals in the marker chromosomes suggested that they had arisen by a break-fusion-bridge (BFB) mechanism.
authors.affiliation: Department of Cell and Molecular Biology-Genetics, Göteborg University, Göteborg, Sweden. Asa.Sjoling@gen.gu.se
authors.forename: A
authors.initials: A
authors.lastname: Sjöling
authors.forename: H
authors.initials: H
authors.lastname: Lindholm
authors.forename: E
authors.initials: E
authors.lastname: Samuelson
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: T K
authors.initials: TK
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Tanigami
authors.forename: G
authors.initials: G
authors.lastname: Levan
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D051356:Cortactin; D019938:Cyclin D1 / Q000235:genetics; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics*; D005784:Gene Amplification; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D051356:Cortactin; C495869:Cttn protein, mouse; C495870:Cttn protein, rat; C489197:Fgf3 protein, mouse; C489199:Fgf3 protein, rat; D051518:Fibroblast Growth Factor 3; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; C112971:fibroblast growth factor 14; D019938:Cyclin D1; D015127:9,10-Dimethyl-1,2-benzanthracene; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053614:Janus Kinase 2