Transgenic oncogene mice. Tumor phenotype predicts genotype.

The hypothesis that oncogenes influence tumor phenotype was tested by examining slides from 607 mammary tumors from 407 transgenic mice bearing the ras, myc, and/or neu oncogenes. Most tumors (91%) had patterns (phenotypes) that could not be classified by Dunn's standard nomenclature. The nonstandard tumors were described as eosinophilic small cell (SC), basophilic large cell (LC), or pale intermediate cell (IC). The SC tumor was associated with ras, the LC was associated with myc, and the IC was associated with neu, with specificities more than .90 and sensitivities ranging from .99 to .48. Thus, the tumor phenotype could be used to predict which oncogene was present in the animal. The presence of myc in combination with either ras or neu resulted in the predominance of LC tumors and accelerated tumorigenesis. The combination of ras and neu resulted in a decreased tumor incidence. Thus, knowledge of the oncogenes that were present could be used to predict the natural history of the disease.