The role of chromosome 15 in murine leukemogenesis. II. Relationship between tumorigenicity and the dosage of lymphoma vs. normal‐parent‐derived chromosomes 15 in somatic cell hybrids

Somatic cell hybrids were generated between an MCF‐vi‐rus‐induced 15‐trisomic T‐cell lymphoma of AKR origin with a proviral insertion near the c‐myc locus, and normal diploid fibroblasts or lymphocytes of CBAT6T6 origin. Three lymphoma/fibroblast fusions were performed. Six independently‐derived clones from 2 fusions were tested for tumorigenicity. Three of the 6 clones were weakly malignant (take incidence 20% below), and 3 were strongly malignant (take incidence over 80%). All 3 lymphoma/lymphocyte hybrids and 6 derived clones were strongly malignant. All hybrids contained a nearly complete chromosomal complement of both parental cells. This was confirmed at the molecular level by determining the ratio of germ‐line (G) vs. rearranged (R) myc‐carrying Eco RI fragments that showed the expected 1.9–2.7:1 proportion. Malignant segregants selected from the weakly malignant lymphoma/fibroblast hybrids by in vivo inoculation showed changed 15‐chromosome ratios. Four out of the 6 clones showed amplification of the lymphoma‐derived 15‐chromosome that carries the R‐myc fragment and a concomitant decrease in the average number of the G‐myc‐carrying chromosomes. This was deduced from the fact that the G:R ratio was between 2 and 3:1 in the in vitro hybrids but became inverted (1:2–3) in the tumors. Two tumors showed no amplification of R‐myc. C‐myc was decreased. One of these tumors showed a change in the G:R ratio from 2.5:1.0 to 1.2:1.0, while the other was essentially unchanged (1.9:1.0 in the in vitro clone and 2.2:1.0 in the derived tumor). These findings support the notion that both the amplification of the lymphoma‐derived 15‐chromosome with the retro virally rearranged c‐myc carrying fragment and/or the loss of the G‐myc‐carrying 15‐chr can contribute to the tumorigenic potential of the hybrids.