Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma

Resistance to the transforming growth factor-beta (TGF-beta) is a frequentl y found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a poss ibility that constitutive activation of the anti-Smads by a somatic mutatio n may impair the TGF-beta signaling pathway. We tested this hypothesis by s creening the entire coding sequences of these anti-Smads for mutations in 5 2 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand confomation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 a nd Smad7 genes are not the main cause of the TGF-beta resistance in human H CC.