Double Minutes Arise from Circular Extrachromosomal DNA Intermediates Which Integrate into Chromosomal Sites in Human HL-60 Leukemia Cells

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1990 Jun 1

PMID 2189894

Citations 29

Authors

D D Von Hoff

B Forseth

C N Clare

K L Hansen

D VanDevanter

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Breakage fusion bridge cycles drive high oncogene copy number, but not intratumoral genetic heterogeneity or rapid cancer genome change.

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Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications.

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Extrachromosomal circular DNA in cancer drug resistance and its potential clinical implications.

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Extrachromosomal circular DNA: biogenesis, structure, functions and diseases.

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