LOSS OF IMPRINTING IN NORMAL TISSUE OF COLORECTAL-CANCER PATIENTS WITH MICROSATELLITE INSTABILITY

Loss of imprinting (LOI) is an epigenetic alteration of some cancers i nvolving loss of parental origin-specific expression of imprinted gene s. We observed LOI of the insulin-like growth factor-ii gene in twelve of twenty-seven informative colorectal cancer patients (44%), as well as in the matched normal colonic mucosa of the patients with LOI in t heir cancers, and in peripheral blood samples of four patients. Ten of eleven cancers (91%) with microsatellite instability showed LOI, comp ared with only two of sixteen tumors (12%) without microsatellite inst ability (P< 0.001). Control patients without cancer showed LOI in colo nic mucosa of only two of sixteen cases (12%, P < 0.001) and two of fi fteen blood samples (13%, P < 0.001). These data suggest that LOI in t umor and normal tissue identifies most colorectal cancer patients with microsatellite instability in their tumors, and that LOI may identify an important subset of the population with cancer or at risk of devel oping cancer.