Molecular Approach to the Etiology of Human Cancer
Abstract DNA-RNA hybridization was used to explore whether human neoplasias contain RNA molecules having sequence homologies to those of the RNA tumor viruses known to cause similar diseases in animals. The pattern of specific RNA's found in the human tumors showed a remarkable concordance with the predictions deducible from the animal systems. Thus, human breast cancer contains RNA homologous only to that of the murine mammary tumor virus. Human leukemias, sarcomas, and lymphomas (including Hodgkin's and Burkitt's lymphomas) all contain RNA with sequence homology to the murine leukemia virus and not to murine mammary tumor virus RNA. Finally, as in the case of the mouse, none of the human tumors examined contains RNA in sequence to that of the avian myeloblastosis virus. The RNA detected in all of the human neoplasias was demonstrated to be of high molecular weight (1 × 107 daltons) and encapsulated with a reverse transcriptase in particles having densities between 1-16 and 1.19 g/ml. Further, the RNA of these human tumor particles was related in sequence to the murine viruses that cause the corresponding neoplasias in mice. Thus, four features diagnostic for the murine oncogenic viruses are satisfied by the particles found in the human cancers. Finally, it was shown by “recycling” experiments that the DNA from human leukemic cells and from lymphomatous tissue contained particle-related sequences that could not be detected in normal DNA. This finding was further substantiated by studies with identical twins in which it was shown that the leukemic twin contained particle-related sequences that could not be detected in the leukocytes of his identical healthy sibling. These findings are inconsistent with hypotheses that require chromosomal transmission in the germ line of complete copies of the information required to produce malignancy and the associated virus particles.