Identification of Notch1 as a frequent target for provirus insertional mutagenesis in T-cell lymphomas induced by leukemogenic mutants of mouse mammary tumor virus

In contrast to wild-type mouse mammary tumor virus (MMTV), the MMTV mutants with specific deletions in the U3 region of their long terminal repeats ca use T-cell lymphomas. In 30% of T-cell lymphomas arising in BALB/c mice inf ected with MLA-MMTV, a Leukemogenic MMTV mutant, we have found that MMTV pr oviruses were integrated into a short region of the Notch1 genome, so that truncated Notch1 transcripts encoding the transmembrane and the cytoplasmic domains of Notch1 protein could be expressed. Thus, Notch1 is a major targ et of provirus insertional mutagenesis in these T-cell lymphomas.