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Smad2 and Smad4 gene mutations in hepatocellular carcinoma

Oncogene volume 18, pages 4879–4883 (1999)Cite this article

Abstract

TGF-β is a negative regulator of liver growth. Smad family of genes, as mediators of TGF-β pathway, are candidate tumor suppressor genes in hepatocellular carcinoma (HCC). We studied 35 HCC and non-tumour liver tissues for possible mutations in Smad2 and Smad4 genes. Three tumours displayed somatic mutations; two in Smad4 (Asp332Gly and Cys401Arg) and one in Smad2 (Gln407Arg) genes. All three mutations were A:T → G:C transitions suspected to result from oxidative stress as observed in mitochondrial DNA. These observation demonstrate that TGF-β pathway is altered in hepatocellular carcinoma.

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Acknowledgements

This work was supported by grants from TUBITAK and TWAS. We thank Dr Marie Ricciardone and Ms Birsen Cevher for help in DNA sequence analyses and Mrs Lutfiye Mesci for oligonucleotide synthesis. We also thank Dr SE Kern for providing us with exon-intron boundary sequence information for Smad4 gene.

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Author notes

  1. A Romano

    Present address: Institute of Molecular Pathology, Vienna, A-1030, Austria

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Bilkent University, Bilkent, Ankara, 06533, Turkey

    M C Yakicier, M B Irmak, A Romano & M Ozturk

  2. University of The Witwatersrand, Johannesburg, South Africa

    M Kew

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  1. M C Yakicier
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Yakicier, M., Irmak, M., Romano, A. et al. Smad2 and Smad4 gene mutations in hepatocellular carcinoma. Oncogene 18, 4879–4883 (1999). https://doi.org/10.1038/sj.onc.1202866

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