Mutational analysis of transgenic mouse B cell lymphomas: indication of a Trp53-independent pathway in tumor...

Deregulated myc, bcl-2 and/or TP53 gene expression is associated with non-Hodgkin's B cell lymphomas (B-NHLs). Emu-N-myc transgenic mice that misexpress N-myc protein and carry a non-disrupted bcl-2 gene develop indolent B cell lymphomas reminiscent of the B-NHL, follicular lymphoma. Tumors from mice with end-stage disease exhibited discrete, nodular lesions as well as areas of diffuse tumor likely due to coalescence of enlarged follicles. Tumor DNAs were screened for mutations in the Trp53 gene, the murine homologue of the TP53 gene, which participates in B cell differentiation and survival. By PCR-based sequence analyses, we determined there were no mutations in exons 5-8, the common sites of TP53 mutation in B-NHLs. These findings suggested that disease progression in our novel murine lymphoma model may proceed via a Trp53-independent pathogenetic pathway.