SPONTANEOUS INTESTINAL CARCINOMAS AND SKIN NEOPLASMS IN MSH2-DEFICIENT MICE

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