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Journal of Virology, October 2000, p. 9786-9791, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Shin-ichi Yanagawa,1,* Jong-Seo Lee,1,dagger Kazuhiro Kakimi,1,Dagger Yukihiro Matsuda,1 Tasuku Honjo,2 and Akinori Ishimoto1

Department of Viral Oncology, Institute for Virus Research,1 and Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine,2 Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

Received 27 March 2000/Accepted 24 July 2000

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 cause T-cell lymphomas. In 30% of T-cell lymphomas arising in BALB/c mice infected with MLA-MMTV, a leukemogenic MMTV mutant, we have found that MMTV proviruses 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 target of provirus insertional mutagenesis in these T-cell lymphomas.

* Corresponding author. Mailing address: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-3996. Fax: 81-75-751-3995. E-mail: syanagaw{at}virus.kyoto-u.ac.jp.

dagger Present address: Department of Pathology, Harvard Medical School, Boston, MA 02115.

Dagger Present address: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.

Journal of Virology, October 2000, p. 9786-9791, Vol. 74, No. 20
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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