Advertisement
Research Article Free access | 10.1172/JCI114650
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Find articles by Von Hoff, D. in: JCI | PubMed | Google Scholar
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Find articles by Forseth, B. in: JCI | PubMed | Google Scholar
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Find articles by Clare, C. in: JCI | PubMed | Google Scholar
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Find articles by Hansen, K. in: JCI | PubMed | Google Scholar
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Find articles by VanDevanter, D. in: JCI | PubMed | Google Scholar
Published June 1, 1990 - More info
Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63-72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5;17)(q11.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients' tumors.
Images.