HETEROGENEITY OF B-LYMPHOID TUMORS IN E-MU-MYC TRANSGENIC MICE

The clinically important issue of tumor heterogeneity was studied in C 57BL/6-E mu-myc transgenic mice, which provide a genetically uniform m odel system in which all animals eventually develop B cell lymphomas a fter additional genetic changes beyond enforced expression of the tran sgenic oncogene. Three different approaches were compared for discerni ng the cellular and genetic homogeneity of these tumors, Analysis of I gh gene rearrangement showed mainly monoclonality and only infrequent oligoclonality in the tumors from a given animal, In contrast, cytogen etic examination indicated a substantial degree of heterogeneity in th e tumors from a given animal and showed that a wide variety of seconda ry genetic changes occur in E mu-myc transgenic mice, Flow cytometry o f DNA content also revealed a high degree of heterogeneity within and among the tumor masses from single E mu-myc mice. Estimates of tumor h eterogeneity revealed by these three techniques often did not coincide , indicating that these different approaches reflect distinct cellular parameters, Transgenic E mu-myc mice additionally homozygous for the scid mutation displayed enhanced levels of secondary genetic changes t hat were valuable for the methodological comparisons performed here, a nd demonstrated that the extent of tumor heterogeneity can be influenc ed by specific genes other than the primary E mu-myc transgene, In sum mary, a combination of methodologies appears to be required to reveal the full extent of tumor heterogeneity within a single individual. (C) 1996 Wiley-Liss, Inc.