The role of chromosome 15 in murine leukemogenesis. I. Contrasting behavior of the tumor vs. normal parent-derived chromosomes No. 15 in somatic hybrids of varying tumorigenicity.

G-banding analysis was carried out on a series of hybrids derived from the fusion of a chromosome 15-trisomic murine T-cell leukemia of AKR origin and normal diploid fibroblasts or lymphocytes of the CBT6T6 strain. Due to the 14;15 translocation involved in the generation of the T6 marker, the chromosomes No. 15 and 14 derived from the normal and the tumor parent can be distinguished cytogenetically. Highly tumorigenic, in vitro maintained hybrids, and high-tumorigenic segregants of originally low-tumorigenic in vitro hybrids, selected by in vivo passage, showed a similar cytogenetic pattern. It was characterized by the amplification of the tumor-derived chromosomes No. 15 from the expected 3 to 5.5 +/- 0.2 copies and a concomitant decrease of the normal derived T(14;15)6 from 2 copies to 0.9 +/- 0.2. All other autosomes except No. 14 showed only minor random variations, around the expected number of 4 copies. The tumor-derived chromosome 14 was amplified from the expected 2 to 3 copies. The low-tumorigenic hybrids showed the opposite pattern with a decrease in the number of the tumor-derived 15 chromosome from 3 to 2.6 +/- 0.1 and the maintenance of the two normal parent derived T(14;15)6 chromosomes. These findings suggest the existence of a qualitative difference between the 15 chromosomes derived from the tumor vs. the normal parent, due to mutation or proviral DNA insertion in the tumor-derived homologue. Amplification of the change locus and a decrease in the dosage of its normal counterpart appear to favor tumorigenicity.