Mutator phenotype in a subset of chronic lymphocytic leukemia

The replication error phenotype (RER⁺), characterized by widespread microsatellite instability, is an important feature of tumors from patients with hereditary nonpolyposis colorectal carcinoma (HNPCC). This widespread instability affects repeat tracts of all lengths and is usually attributed to mutations of critical mismatch repair genes. Recently, several reports described occasional microsatellite alterations in tumors not associated with HNPCC. However, s true mutator phenotype (RER⁺) is very rare outside of HNPCC-associated malignancies. We examined 29 cases of chronic lymphocytic leukemia (CLL), the most common leukemia in the Western world for evidence of microsatellite instability. We identified a mutator phenotype in (2/29) 7% of the cases studied. These data suggest that the mismatch repair pathway may be altered in at least a subset of patients with CLL.