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Evolution of karyotypic abnormalities and C-MYC oncogene amplification in human colonic carcinoma cell lines
Authors:C. C. Lin  Kari Alitalo  Manfred Schwab  Donna George  Harold E. Varmus  J. Michael Bishop
Affiliation:(1) Departments of Pediatrics and Medical Biochemistry, University of Calgary, T2N 4N1 Calgary, Alberta, Canada;(2) Department of Virology, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki 29, Finland;(3) Department of Microbiology and Immunology and G.W. Hooper Foundation, University of California, 94143 San Francisco, CA, USA;(4) Department of Human Genetics, University of Pennsylvania School of Medicine, 19104 Philadelphia, Pa, USA;(5) Present address: Cytogenetics Laboratory, Department of Laboratory Medicine, 5B4.49 WC Mackenzie Heath Science Centre, University of Alberta, T6G 2R7 Edmonton, Alberta, Canada
Abstract:Cell lines (COLO 320 DM and COLO 320 HSR), established from a human neuroendocrine tumor, contain an amplified cellular oncogene (c-myc). We have previously shown that the homogeneously staining regions (HSRs) of a marker chromosome in the COLO 320 HSR cells that evolved in culture from COLO 320 DM cells contain amplified c-myc. Molecular hybridization in situ has now been used to demonstrate that the HSRs are on both arms of what was once an X chromosome. We also show that amplified c-myc copies are present in the isolated double minute chromosomes (DMs) of the COLO 320 DM cells that were characteristic of the tumor cells initially established from the patient. The results suggest that the amplified c-myc appeared first as DMs and was subsequently transposed to engender HSRs on an X chromosome. The initial COLO 320 tumor cell may have acquired two ldquoearly replicatingrdquo (i.e., active) X chromosomes and lost the ldquolate replicatingrdquo (i.e., inactive) X.
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