SJL mice are an inbred strain with a high incidence of spontaneous
lymphomas of the B-cell type. We used molecular markers of clonality to study the process of
tumor progression of SJL
lymphomas in vivo. This was accomplished at time intervals ranging from 2 to 116 days by initial partial
splenectomy (biopsy) followed by spleen sampling at the time of killing (autopsy).
Immunoglobulin heavy chain (IgH) gene rearrangement and murine leukemia virus (MuLV) proviral integration patterns were used to study the clonal identities of the sequential
tumor pairs in 11 informative mice by Southern blot hybridization. Of these 11 mice, 5 showed the same number of IgH gene rearrangement bands in the matched biopsy-autopsy samples, indicating the persistence of the original lesions. In 2 of 11 mice, a decrease in the number of IgH gene rearrangement bands was seen, consistent with a process of clonal selection in the original oligoclonal population. Another 2 of 11 mice showed an increase in the IgH gene rearrangement bands, indicating the emergence of either a new unrelated clone or, less likely, a subclone with secondary IgH gene rearrangement. The remaining two mice showed differences between the patterns in biopsy and autopsy samples, as assessed by IgH gene rearrangement and the proviral integration analysis. This finding suggests that the biopsied
tumor had regressed and new clones had emerged.
Tumor development was also associated with an increase in the number of clonal MuLV insertions in all mice except one, in which no non-germline integration band was detected. Of 11 mice, 5 showed an increase in the extent of
tumor involvement by microscopic examination of the biopsy and autopsy samples; 3 showed a decrease, whereas 2 showed no change. A change in
tumor morphology toward a more dedifferentiated appearance was found in only 1 of 11 mice. Overall, the results did not show a single paradigm that
tumor progression followed, rather they indicated a complex and dynamic process of clonal evolution, which is likely to be a major feature of
lymphoma progression in vivo.