A TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR-TYPE-II GENE MUTATION COMMON IN COLON AND GASTRIC BUT RARE IN ENDOMETRIAL CANCERS WITH MICROSATELLITE INSTABILITY

We have recently demonstrated that mutation of the transforming growth factor-beta (TGF-beta) receptor type II (RII) gene is characteristic of colon cancers exhibiting microsatellite instability or replication errors (RER+), Moreover, we have shown that RII mutations in these RER + colon cancers are characteristically frameshift mutations within a 1 0-bp polyadenine repeat present in the RII-coding region, We now show that RII gene mutations in this polyadenine repeat are also commonly p resent in RER+ gastric cancers (71%). In contrast, we find these same RII gene mutations are distinctly uncommon in RER+ endometrial cancers (17%, P < 0.02), These results suggest that RII gene mutations confer a growth advantage and are selected for in RER+ cancers of both the u pper and lower gastrointestinal tract, The genesis of RER+ endometrial tumors must, however, be by a different route.