We have recently demonstrated that mutation of the transforming growth factor-β (TGF-β) 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 10-bp polyadenine repeat present in the RII-coding region. We now show that RII gene mutations in this polyadenine repeat are also commonly present 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 upper and lower gastrointestinal tract. The genesis of RER+ endometrial tumors must, however, be by a different route.
Supported by NIH Grants CA57208 and P01 CA51183 (S. D. M.); P30 CA4370301 to the Case Western Reserve University Cancer Center; CA09320 (R. P.), CA68769 (K. O.), CA66720 (L. H.), CA62924 (K. W. K.), and CA35494 (B. V.); American Cancer Society Grants FRA-451 (S. M.), RD-381 (H. L.), and EDT-84 (H. L.); Council for Tobacco Research Grant 1297ER1 (H. L.); Korea Science and Engineering Foundation Grant KOSEF-SRC-56-CRC-94K3-0401-01-03-3 (Y-J. B., J-G. P.); and by grants from the Ohio Cancer Research Associates (S. M.) and the Clayton Fund (B. V.). B. V. is an investigator of the Howard Hughes Medical Institute.