The zyxw ets Genes in Cells and Viruses: Implications for Leukemias and Other Human Diseases zyx TAKIS S. PAPAS: NARAYAN K. BHAT: ROBERT J. FISHER: SHIGEYOSHI FUJIWARA: STEPHEN D. SHOWALTER: DENNIS K. WATSON: MARTIN ZWEIG: AND RICHARD ASCIONE" "Laboratory zyxwv of Molecular Oncology National Cancer Institute Frederick Maryland 21 zyxw 701-1013 bDepartment of Biology The Johns Hopkins University 34th and Charles Streets Baltimore, Maryland 21 218 'Nucleic Acid and Protein Synthesis Laboratory Program Resources, Inc. P. 0. Box B Frederick, Maryland 21 701-1013 dBionetics Research, Inc. P. 0. Box B Frederick, Maryland 21 701-1013 THOMAS T. CHEN,~ GARRETT DUBOIS: LOUIS J. PRIBYL: NICOLETTA SACCHI: ARUN SETH! One of the most interesting scientific challenges of our time has been to understand the spectrum of oncogenic changes necessary to commit normal cells to a neoplastic life-style. On the molecular level, this enigmatic quest centers upon our understanding the essential ingredients needed to control cell growth (and its coordinate processes), as well as to maintain the normal differentiated pattern of expression for specific genes. Another, perhaps simpler, approach to this difficult challenge would be to examine the genetic changes resulting from the introduction of a known acute retroviral transform- ing sequence capable of eliciting a malignant cellular phenotype in vitro and neoplastic disease in vivo. Through the application of the powerful technique of recombinant technology application in the study of model retrovirus systems, the precise DNA sequences responsible for cellular transformation have been identified and studied. Thus, the employment of acute retroviruses as tools to identify a select cohort of genes capable of malignant transformation has been most fruitful. More important, from this study came a realization that this category of genes, the viral oncogenes, were capable of establishing and maintaining the transformed state, as well as the recognition that these genes were derivatives of a limited population of normal cellular genes, the proto-oncogenes, that can be captured and modified by the viral transduction process. These homologous genes, now numbering several dozen, are found distributed in the genomes of almost all vertebrates and of some invertebrate species, as well as of a few more primitive single-cell species. zyxwv 171