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JNCI Journal of the National Cancer Institute 1990 82(23):1815-1821; doi:10.1093/jnci/82.23.1815
© 1990 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 82, No. 23, 1815-1821, December 5, 1990
© 1990 Oxford University Press

Ability of Circular Extrachromosomal DNA Molecules to Carry Amplified MYCN Protooncogenes in Human Neuroblastomas In Vivo

Donald R. VanDevanter, Victoria D. Piaskowski, James T. Casper, Edwin C. Douglass, Daniel D. Von Hoff*

Clinical Research Division, Tumor Institute, Swedish Hospital Medical Center Seattle, Wash
Midwest Children's Cancer Center, Medical College of Wisconsin, Children’s Hospital of Wisconsin Milwaukee, Wis
Department of Hematology/Oncology, St. Jude Children‘s Research Hospital and Division of Hematology/Oncology, Department of Pediatrics, The University of Tennessee College of Medicine Memphis, Tenn
Division of Medicine/Oncology, University of Texas Health Science Center at San Antonio (UTHSC-SA) San Antonio, Tex

*Correspondence to: Daniel D. Von Hoff, MD, Division of Medicine/Oncology, UTHSC-SA, 7703 Floyd Curl Dr, San Antonio, TX 78284–7884.

Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification. [J Natl Cancer Inst 82:1815–1821, 1990]


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