Mutational spectrum of β-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas

Ken Taniguchi, Lewis R. Roberts, Ileana N. Aderca, Xiangyang Dong, Chiping Qian, Linda M. Murphy, David M. Nagorney, Lawrence J. Burgart, Patrick C. Roche, David I. Smith, Julie A. Ross, Wanguo Liu

Research output: Contribution to journalArticlepeer-review

386 Scopus citations

Abstract

Activation of Wnt signaling through β-catenin mutations contributes to the development of hepatocellular carcinoma (HCC) and hepatoblastoma (HB). To explore the contribution of additional Wnt pathway molecules to hepatocarcinogenesis, we examined β-catenin, AXIN1 and AXIN2 mutations in 73 HCCs and 27 HBs. β-catenin mutations were detected in 19.2% (14 out of 73) HCCs and 70.4% (19 out of 27) HBs. β-catenin mutations in HCCs were primarily point mutations, whereas more than half of the HBs had deletions. AXIN1 mutations occurred in seven (9.6%) HCCs and two (7.4%) HBs. The AXIN1 mutations included seven missense mutations, a 1 bp deletion, and a 12 bp insertion. The predominance of missense mutations found in the AXIN1 gene is different from the small deletions or nonsense mutations described previously. Loss of heterozygosity at the AXIN1 locus was present in four of five informative HCCs with AXIN1 mutations, suggesting a tumor suppressor function of this gene. AXIN2 mutations were found in two (2.7%) HCCs but not in HBs. Two HCCs had both AXIN1 and β-catenin mutations, and one HCC had both AXIN2 and β-catenin mutations. About half the HCCs with AXIN1 or AXIN2 mutations showed β-catenin accumulation in the nucleus, cytoplasm or membrane. Overall, these data indicate that besides the approximately 20% of HCCs and 80% of HBs with β-catenin mutations contributing to hepatocarcinogenesis, AXIN1 and AXIN2 mutations appear to be important in an additional 10% of HCCs and HBs.

Original languageEnglish (US)
Pages (from-to)4863-4871
Number of pages9
JournalOncogene
Volume21
Issue number31
DOIs
StatePublished - 2002

Keywords

  • AXIN1
  • AXIN2
  • Hepatoblastoma
  • Hepatocellular carcinoma
  • Mutations
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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