Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3.
We screened 75 primary hepatocellular carcinomas for somatic mutations in the entire coding region of the beta-catenin gene. We detected somatic mutations in 14 tumors; 12 were considered to cause amino acid substitutions and 2 were interstitial deletions of 51 or 195 nucleotides of genomic DNA, corresponding to exon 3. Among the 12 point mutations, 6 occurred at potential serine/threonine phosphorylation residues of codons 33, 41, or 45. The remaining six tumors contained a mutation at codon 32 (aspartic acid) or 34 (glycine), flanking to the serine residue at codon 33. By Western blot analysis, we confirmed accumulation of beta-catenin in five tumors for which frozen tissues were available; the five included tumors in which amino acid alterations had occurred at codons 32, 34, or 45, and one with a 17-amino acid deletion. Our results suggested that accumulation of beta-catenin due to amino acid substitutions at potential serine/threonine phosphorylation residues or at their neighboring codons or interstitial deletions involving exon 3 could contribute to hepatocellular carcinogenesis.
Miyoshi
Y
Y
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Japan.
Iwao
K
K
Nagasawa
Y
Y
Aihara
T
T
Sasaki
Y
Y
Imaoka
S
S
Murata
M
M
Shimano
T
T
Nakamura
Y
Y
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin