MUTATION ANALYSIS OF THE TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR IN SPORADIC HUMAN CANCERS OF THE PANCREAS, LIVER, AND BREAST

The transforming growth factor beta (TGFbeta) binds the type II TGFbet a growth factor receptor (TGFbeta RII) to inhibit growth of most epith elial tissues. Most human colon cancers with microsatellite instabilit y have frameshift mutations in two microsatellites within the TGFbeta RII coding region; such mutations truncate the receptor to produce res istance to TGFbeta. To investigate this pathway in other tissues, we s urveyed sporadic human cancers of the pancreas, liver and breast to de termine the frequency of microsatellite mutations in the TGFbeta RII. We amplified genomic DNA segments containing two microsatellites plus 72% of domain XI of the serine-threonine kinase region. SSCP analysis showed no evidence of mutation in 32 sporadic cancers (12 pancreas, 10 liver, and 10 breast). We conclude that microsatellite mutations in T GFbeta RII are uncommon in sporadic tumors of the pancreas, liver and breast. (C) 1996 Academic Press, Inc.