Biallelic inactivation of theAPC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli

Abstract

BACKGROUND Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC. METHODS Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene. RESULTS A somatic one–base pair deletion at codon 568 was identified in the wild‐type allele of the APC gene. CONCLUSIONS To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP. Cancer 2001;92:332–9. © 2001 American Cancer Society.

Hepatocellular adenoma containing hepatocellular carcinoma in a male patient with familial adenomatous polyposis coli: Report of a case

“…A biallelic inactivation of the APC gene has also recently been observed in FAP-associated extracolonic tumors, particularly in two cases of HCA and one case of HCC that developed in FAP patients. [8][9][10] We believe this is the fi rst case of HCC within HCA occurring in a patient with FAP. We also investigated whether genetic alterations occurred during liver Reprint requests to: Y. Toiyama Received: March 2, 2010 / Accepted: October 20, 2010 tumorigenesis either via β-catenin activation or HNF1α inactivation, thus leading to HCC and HCA, respectively, in this patient.…”

Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis

“…Somatic APC mutations are rare events in HCC, but it was recently reported that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with familial adenomatous polyposis and a known germline mutation of the APC gene at codon 208 [43]. E-cadherin, the cytoplasmic anchor protein of β-catenin, is rarely mutated in HCC.…”

Liver-targeted disruption ofApcin mice activates β-catenin signaling and leads to hepatocellular carcinomas

“…Interestingly, no somatic mutation of the APC gene and no loss of heterozygosity of the 5q21 APC locus have been described in HCC, even though this event is implicated in Ͼ80% of colorectal cancers (5,6). However, there are data implicating a loss of function of APC in liver carcinogenesis: infrequent hepatoblastomas have been described (7,8) and two cases of HCC have been reported (9,10) in familial adenomatous polyposis patients carrying a germ-line heterozygous mutation of the APC gene.…”