Genetic inactivation of the APC gene contributes to the malignant progression of sporadic hepatocellular carcinoma: A case report

Hiroto Katoh, Tatsuhiro Shibata, Akiko Kokubu, Hidenori Ojima, Tomoo Kosuge, Yae Kanai, Setsuo Hirohashi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Although activated Wnt/β-catenin pathway is considered to be one of the main driving forces of hepatocarcinogenesis, no somatic mutations of the adenomatous polyposis coli (APC) gene have been found in sporadic hepatocellular carcinoma (HCC) to date. Here we present a case of a sporadic nodule-in-nodule-type HCC that provides the first evidence that biallelic genetic inactivation of the APC gene contributed to the development of the tumor. High-density array-based comparative genomic hybridization (aCGH) was performed to clarify genome-wide chromosomal structural alteration profiles of both early and advanced components of this nodule-in-nodule HCC. aCGH analysis revealed a chromosomal loss of the APC gene locus only in the inner advanced component of this tumor. Direct sequencing of the remaining allele revealed a nonsense mutation at codon 682 in the Armadillo repeats, resulting in a truncated protein that lacked all of the β-catenin-binding motifs. Nonsense mutations at this location are rare among other types of cancer. In conclusion, combined with an immunohistochemical analysis of the β-catenin protein, this case provides the first evidence that genetic inactivation of the APC gene can play a significant role in the progression of sporadic HCC, probably by activating the Wnt/β-catenin pathway.

Original languageEnglish
Pages (from-to)1050-1057
Number of pages8
JournalGenes Chromosomes and Cancer
Volume45
Issue number11
DOIs
Publication statusPublished - 2006 Nov
Externally publishedYes

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APC Genes
Catenins
Hepatocellular Carcinoma
Wnt Signaling Pathway
Comparative Genomic Hybridization
Nonsense Codon
Armadillos
Neoplasms
Codon
Alleles
Genome
Mutation
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Genetic inactivation of the APC gene contributes to the malignant progression of sporadic hepatocellular carcinoma : A case report. / Katoh, Hiroto; Shibata, Tatsuhiro; Kokubu, Akiko; Ojima, Hidenori; Kosuge, Tomoo; Kanai, Yae; Hirohashi, Setsuo.

In: Genes Chromosomes and Cancer, Vol. 45, No. 11, 11.2006, p. 1050-1057.

Research output: Contribution to journalArticle

Katoh, Hiroto ; Shibata, Tatsuhiro ; Kokubu, Akiko ; Ojima, Hidenori ; Kosuge, Tomoo ; Kanai, Yae ; Hirohashi, Setsuo. / Genetic inactivation of the APC gene contributes to the malignant progression of sporadic hepatocellular carcinoma : A case report. In: Genes Chromosomes and Cancer. 2006 ; Vol. 45, No. 11. pp. 1050-1057.
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