Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity

Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8165-9. doi: 10.1073/pnas.89.17.8165.


Oncogene amplification has been observed in a broad spectrum of human tumors and has been associated with a poor prognosis for patients with several different types of malignancies. Importantly, at biopsy, the amplified genes localize to acentric extrachromosomal elements such as double-minute chromosomes (DMs) in the vast majority of cases. We show here that treatment of several human tumor cell lines with low concentrations of hydroxyurea accelerates the loss of their extrachromosomally amplified oncogenes. The decreases in MYC copy number in a human tumor cell line correlated with a dramatic reduction in cloning efficiency in soft agar and tumorigenicity in nude mice. No effect on gene copy number or tumorigenicity was observed for a closely related cell line containing the same number of chromosomally amplified MYC genes. One step involved in the accelerated loss of extrachromosomal elements is shown to involve their preferential entrapment of DMs within micronuclei. The data suggest that agents that accelerate the loss of extrachromosomally amplified genes could provide valuable tools for moderating the growth of a large number of human neoplasms.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / ultrastructure
  • Chromosome Aberrations / pathology
  • Chromosome Disorders
  • Extrachromosomal Inheritance / drug effects*
  • Gene Amplification*
  • Genes, myc*
  • Humans
  • Hydroxyurea / pharmacology
  • In Vitro Techniques
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / ultrastructure
  • Tumor Cells, Cultured


  • Hydroxyurea