Retroviruses cause tumors in experimental animals via a number of diverse mechanisms. One group of viruses induces transformation by introduction of a viral gene (v-onc) derived from a normal cellular gene (c-onc) (1–3). In general, acquisition of the c-onc gene is accompanied by various alterations, including single base changes and deletions, and fusions with other cellular or viral genes (4). The oncogenes which have been isolated from viruses number about twenty, of which the majority are, or are related to, genes encoding bonafide protein tyrosine kinases (2,4,5). the function of another group of genes, including fos, myb, myc and ski, is not determined, but their localization in the nucleus suggests that they may play a role in control of gene expression.

A remarkable discovery of the past few years is the fact that many acutely oncogenic retroviruses contain sequences as an integral part of their genome which have homologs in normal cells (1). Acquisition of normal cellular sequences by retroviruses, usually at the expense of genes required for replication, enables them to induce neoplasias in vivo and transformation of a wide variety of cells in vitro (2). Such acquired cellular sequences have been termed as cellular protooncogenes or c-onc while their viral homologs are referred to as viral oncogenes or v-onc. To date nearly 20 unique v-onc genes have been identified which have cellular counterparts (3). Some c-onc genes have been identified by DNA transfection studies (4). The c-onc gene sequences are remarkably well conserved during evolution (5).

The complete nucleotide sequence of the c-fos(human) gene, the human cellular homolog of the oncogene (v-fos) of Finkel-Biskis-Jinkins murine osteosarcoma virus, has been determined. The c-fos(human) gene contains four discontinuous regions when compared with the v-fos gene. Three of the discontinuities are flanked by sequences characteristic of introns, while the fourth discontinuity is due to a deletion of 104 base pairs in the v-fos gene. As a consequence of the deletion, the predicted c-fos(human) and v-fos gene products differ at their carboxyl termini. Transcripts of 2.2 kilobases from the c-fos(human) gene have been identified in human cells. The sizes of these transcripts are in close agreement with the size expected from the nucleotide sequence after removal of introns.

A 12.0-kilobase EcoRI restriction fragment containing FBJ murine osteosarcoma virus (FBJ-MSV) proviral DNA was identified in FBJ-MSV-transformed nonproducer rat cells and molecularly cloned in bacteriophage Charon 30 (lambda FBJ-1). A 5.8-kb HindIII fragment containing the entire FBJ-MSV proviral DNA was isolated from lambda FBJ-1 and subsequently subcloned in plasmid pBR322 (pFBJ-2). The DNA from recombinant plasmid pFBJ-2 was able to induce morphological transformation of rat fibroblasts in tissue culture. Transfected cells contained the p55 and p39 antigens specific for cells transformed by FBJ-MSV (T. Curran and N. M. Teich, J. Virol. 42:114-122, 1982). The organization of the FBJ-MSV provirus was analyzed by restriction endonuclease mapping, and a region of nonhomology with the helper virus was delineated. Sequences specific for this region (presumably the viral fos gene) were subcloned and used as a probe to identify related sequences present in the normal genomes of cells from a variety of mammalian species (cellular fos). A single-size (3.4 kilobases long) class of RNA hybridizing to the viral fos probe was identified in FBJ-MSV-transformed cells.

DNA complementary to Moloney murine leukemia viral RNA was annealed with DNA isolated from peripheral leukocytes of twelve patients with leukemia. Six to 10% of the complementary DNA annealed to the DNA of one patient with acute myelogenous leukemia. The level of annealing of the complementary DNA to the other leukemic DNA's did not differ significantly from that to normal human spleen DNA. This result is consistent with reports of occasional positive results from other laboratories, but the significance, especially in reference to a causal role for RNA tumor viruses in human leukemia, remains unclear.

Transformation by human adenoviruses is a process in which only a small fraction of the viral genome is involved. This is most clearly shown by the observation that specific DNA fragments originating from the left-hand end of the genome are able to transform cells in vitro (Graham et al. 1975; van der Eb et al. 1977; van der Eb and Houweling 1977). This is further supported by the finding that rodent cells transformed by human adenovirus types 2 or 5 (Ad2 or Ad5) all contain viral DNA sequences homologous to the left-hand 14% of the genome, whereas some of the lines also contain sequences homologous to other parts of the viral DNA (Gallimore et al. 1974; Sharp et al. 1975; Flint et al. 1976). This indicates that transformation is basically a function of early region 1 (E1), which maps between 1% and 11% in the DNA of all human adenoviral...