MISMATCH REPAIR GENE DEFECTS IN SPORADIC COLORECTAL CANCERS WITH MICROSATELLITE INSTABILITY

Microsatellite instability has been observed in both sporadic and here ditary forms of colorectal cancer. In the hereditary form, this instab ility is generally due to germline mutations in mismatch repair (MMR) genes. However, only one in ten patients with sporadic tumours exhibit ing microsatellite instability had a detectable germline mutation. Mor eover, only three of seven sporadic tumour cell lines with microsatell ite instability had mutations in a MMR gene, and these mutations could occur somatically. These results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability. They also suggest that many sp oradic tumours with microsatellite instability have alterations in gen es other than the four now known to participate in MMR.