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[Cancer Research 56, 3842-3849, August 15, 1996]
© 1996 American Association for Cancer Research
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Spontaneous Intestinal Carcinomas and Skin Neoplasms in Msh2-deficient Mice1

Armin H. Reitmair, Mark Redston, Jian Chun Cai, Tony C.Y. Chuang, Matthew Bjerknes, Hazel Cheng, Kazy Hay, Steven Gallinger, Bharati Bapat and Tak W. Mak2

Departments of Medical Biophysics and Immunology, Ontario Cancer Institute/Amgen Institute, University of Toronto, 510 University Avenue, Toronto, Ontario M5G 2M9 [A. H. R., T. C. Y. C., T. W. M.]; Departments of Pathology and Laboratory Medicine and Surgery, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 1X5 [M. R., J. C. C., K. H., S. G., B. B.]; Department of Anatomy and Cell Biology, University of Toronto, Medical Sciences Building, Toronto, Ontario M5S 1A8 [M. B., H. C.], Canada; and Department of Oncology and Cancer Research Institute, Fujian Union Hospital, Fujian Medical University, Fuzhou 350001, China [J. C. C.]

Hereditary nonpolyposis colorectal cancer is associated with defects in DNA mismatch repair. Here, we characterize tumor susceptibility of the recently described Msh2-deficient mouse model. Within the first year of observation, all homozygous mice succumbed to disease, with lymphomas observed in at least 80% of the cases. The majority (70%) of animals 6 months or older developed intestinal neoplasms associated with APC inactivation. Microsatellite instability was more common in carcinomas than in adenomas, but uncommon in normal tissues. Some animals (7%) developed a variety of skin neoplasms analogous to the Muir-Torre syndrome. Msh2-/- mice implicate a direct role for mismatch repair in several neoplasms with striking phenotypic similarities to humans.

1 This work was supported in part by grants from the National Cancer Institute of Canada (to M. R., B. B., S. G., T. W. M.) and the Medical Research Council of Canada (to M. B., H. C., T. W. M.). A. H. R. was supported by a stipend from the German Academic Exchange Service (DAAD-Doktorandenstipendium aus Mitteln des zweiten Hochschulsonderprogramms).

2 To whom requests for reprints should be addressed.

Received 4/15/96. Accepted 6/10/96.




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