Abstract
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.
Footnotes
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↵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).
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↵2 To whom requests for reprints should be addressed.
- Received April 15, 1996.
- Accepted June 10, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 16
