Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.
To determine the frequency of Wnt/Wingless beta catenin pathway alteration in human hepatocellular carcinoma, a beta catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating beta catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking beta catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between beta catenin mutation status and chromosome segment deletions was studied on a set of 48 hyperploid tumors. Chromosome 1p, 4q and 16p deletions were significantly associated with the absence of beta catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the beta catenin mutated tumors than in the non-mutated tumors (0.12 versus 022). Taken together, these results suggest, the existence of two carcinogenesis mechanisms. The first mechanism implies a beta catenin activating mutation associated with a low rate of loss of heterozygosity. The second mechanism, operating in a context of chromosomal instability, would involve tumor suppressor genes.
Legoix
P
P
Centre d'Etude du Polymorphisme Humain, INSERM U434 Laboratoire de Génétique des Tumeurs, Fondation Jean Dausset/CEPH, Paris, France.
Bluteau
O
O
Bayer
J
J
Perret
C
C
Balabaud
C
C
Belghiti
J
J
Franco
D
D
Thomas
G
G
Laurent-Puig
P
P
Zucman-Rossi
J
J
D000782:Aneuploidy; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D017491:Genes, APC; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C074622:wg protein, Drosophila