Mutation Analysis of the Transforming Growth Factor β Type II Receptor in Sporadic Human Cancers of the Pancreas, Liver, and Breast

Abstract

The transforming growth factor beta (TGFbeta) binds the type II TGFbeta growth factor receptor (TGFbeta RII) to inhibit growth of most epithelial tissues. Most human colon cancers with microsatellite instability have frameshift mutations in two microsatellites within the TGFbeta RII coding region; such mutations truncate the receptor to produce resistance to TGFbeta. To investigate this pathway in other tissues, we surveyed sporadic human cancers of the pancreas, liver and breast to determine 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 TGFbeta RII are uncommon in sporadic tumors of the pancreas, liver and breast.