Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3
Miyoshi, Y.; Iwao, K.; Nagasawa, Y.; Aihara, T.; Sasaki, Y.; Imaoka, S.; Murata, M.; Shimano, T.; Nakamura, Y.
Cancer Research 58(12): 2524-2527
1998
ISSN/ISBN: 0008-5472 PMID: 9635572 Document Number: 489327
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.