title: Smad2 and Smad4 gene mutations in hepatocellular carcinoma.
abstract: TGF-beta is a negative regulator of liver growth. Smad family of genes, as mediators of TGF-beta pathway, are candidate tumor suppressor genes in hepatocellular carcinoma (HCC). We studied 35 HCC and non-tumour liver tissues for possible mutations in Smad2 and Smad4 genes. Three tumours displayed somatic mutations; two in Smad4 (Asp332Gly and Cys401Arg) and one in Smad2 (Gln407Arg) genes. All three mutations were A:T --> G:C transitions suspected to result from oxidative stress as observed in mitochondrial DNA. These observation demonstrate that TGF-beta pathway is altered in hepatocellular carcinoma.
authors.affiliation: Department of Molecular Biology and Genetics, Bilkent University 06533 Bilkent, Ankara, Turkey.
authors.forename: M C
authors.initials: MC
authors.lastname: Yakicier
authors.forename: M B
authors.initials: MB
authors.lastname: Irmak
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.forename: M
authors.initials: M
authors.lastname: Kew
authors.forename: M
authors.initials: M
authors.lastname: Ozturk
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D015398:Signal Transduction; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta