Somatic N-ras Oncogene Activation in a Patient with Acute Myeloblastic Leukemia

Abstract

The recognition that retroviral oncogenes (v-onc) are derived from normal cellular sequences termed proto-oncogenes or c-onc, has led to a search to see whether human proto-oncogenes present in human tumors show alterations in structure or expression. Of particular interest are the activated forms of ras proto-oncogenes; these can be assayed in a biologic test system, since activated ras genes from tumor tissue, but not normal alleles have the ability to transform NIH 3T3 cells in tissue culture [1–4]. The role, if any, of this transforming activity in the natural history of the human tumor is still unknown. The human genome contains three functional ras genes, localized on different chromosomes: H-ras (related to v-ras of Harvey sarcoma virus), K-ras (related to v-ras of Kirsten sarcoma virus), and N-ras, a ras family member identified by nucleic acid hybridization through its relatedness to the former ras genes [5–8]. Activation of ras genes was found to be the result of point mutations altering amino acid 12 of the H-ras or K-ras [11–18] or amino acid 61 of the H-ras or N-ras genes [9, 10, 19].

Friedrich Miescher-Institut, P.O. Box 2543, CH-4002 Basel, and Children’s Hospital, University of Basel, Basel, Switzerland