Abstract
To determine the frequency of Wnt/Wingless β catenin pathway alteration in human hepatocellular carcinoma, a β catenin and APC gene mutation screening was performed in a series of 119 tumors. An activating β catenin mutation in exon 3 was found in 18% of the cases. Among tumors lacking β catenin mutation, no APC mutation has been evidenced in a subset of 30 cases tested. The correlation between β 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 β catenin mutation (P<0.05). Furthermore the Fractional Allelic Loss was significantly smaller in the β 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 β 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bardi G, Johannson B, Pandis N, Heim S, Mandahl N, Andren-Sandberg A, Hagerstrand I and Mitelman F. . 1992 Cancer Genet. Cytogenet. 58: 191–195.
Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S and Thomas G. . 1997 Cancer Res. 57: 1986–1990.
Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR and Ozturk M. . 1990 Proc. Natl. Acad. Sci. USA 87: 1973–1977.
De La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A and Perret C. . 1998 Proc. Natl. Acad. Sci. USA 95: 8847–8851.
De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL. . 1995 Nat. Genet. 11: 447–449.
De Thé H, Marchio A, Tiollais P and Dejean A. . 1987 Nature 330: 667–670.
Graef E, Caselmann WH, Wells J and Koshy R. . 1994 Oncogene 9: 81–87.
Iwao K, Nakamori S, Kameyama M, Imaoka S, Kinoshita M, Fukui T, Ishiguro S, Nakamura Y and Miyoshi Y. . 1998 Cancer Res. 58: 1021–1026.
Marchio A, Meddeb M, Pineau P, Danglot G, Tiollais P, Bernheim A and Dejean A. . 1997 Genes Chromo Cancer 18: 59–65.
Miyoshi Y, Iwao K, Nagasawa Y, Aihara T, Sasaki Y, Imaoka S, Murata M, Shimano T and Nakamura Y. . 1998 Cancer Res. 58: 2524–2527.
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW. . 1997 Science 275: 1787–1790.
Nagai H, Pineau P, Tiollais P, Buendia MA and Dejean A. . 1997 Oncogene 14: 2927–2933.
Olschwang S, Hamelin R, Laurent-Puig P, Thuille B, De Rycke Y, Li YJ, Muzeau F, Girodet J, Salmon RJ and Thomas G. . 1997 Proc. Natl. Acad. Sci. USA 94: 12122–12127.
Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P. . 1997 Science 275: 1790–1792.
Simon D, Munoz SJ, Maddrey WC and Knowles BB. . 1990 Cancer Genet. Cytogenet. 45: 255–260.
Sparks AB, Morin PJ, Vogelstein B and Kinzler KW. . 1998 Cancer Res. 58: 1130–1134.
Tada M, Omata M and Ohto M. . 1990 Cancer Res. 50: 1121–1124.
Takahashi M, Fukuda K, Sugimura T and Wakabayashi K. . 1998 Cancer Res. 58: 42–46.
Wang J, Chenivesse X, Henglein B and Brechot C. . 1990 Nature 343: 555–557.
Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM and Costantini F. . 1997 Cell 90: 181–192.
Acknowledgements
We are very grateful to Claudia de Toma and Jean-Christophe Beaudoin for help in the APC and β catenin mutation screening. We thank Hélène Blons for helpful discussions and critical reading of the manuscript. This work was supported by the Association de la Recherche sur le Cancer and the Ministère de l'Education et de la Recherche.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Legoix, P., Bluteau, O., Bayer, J. et al. Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity. Oncogene 18, 4044–4046 (1999). https://doi.org/10.1038/sj.onc.1202800
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1202800
Keywords
This article is cited by
-
CTNNB1 polymorphism (rs121913407) in circulating tumor DNA (ctDNA) in Egyptian hepatocellular carcinoma patients
Egyptian Liver Journal (2022)
-
Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma
Journal of Gastroenterology (2017)
-
Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma
Modern Pathology (2016)
-
A spatial simulation approach to account for protein structure when identifying non-random somatic mutations
BMC Bioinformatics (2014)
-
Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts
British Journal of Cancer (2014)
