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Mutational and functional analyses reveal that ST7 is a highly conserved tumor-suppressor gene on human chromosome 7q31

Nature Genetics volume 27, pages 392–398 (2001)Cite this article

Abstract

Loss of heterozygosity (LOH) of markers on human chromosome 7q31 is frequently encountered in a variety of human neoplasias, indicating the presence of a tumor-suppressor gene (TSG). By a combination of microcell-fusion and deletion-mapping studies, we previously established that this TSG resides within a critical region flanked by the genetic markers D7S522 and D7S677. Using a positional cloning strategy and aided by the availability of near-complete sequence of this genomic interval, we have identified a TSG within 7q31, named ST7 (for suppression of tumorigenicity 7; this same gene was recently reported in another context and called RAY1). ST7 is ubiquitously expressed in human tissues. Analysis of a series of cell lines derived from breast tumors and primary colon carcinomas revealed the presence of mutations in ST7. Introduction of the ST7 cDNA into the prostate-cancer–derived cell line PC3 had no effect on the in vitro proliferation of the cells, but abrogated their in vivo tumorigenicity. Our data indicate that ST7 is a TSG within chromosome 7q31 and may have an important role in the development of some types of human cancer.

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Figure 1: Long-range genomic organization of ST7.
Figure 2: ST7 mutations in tumor-derived cell lines and primary tumors.
Figure 3: Expression profile of ST7.
Figure 4: Effect of ectopic ST7 expression on in vitro proliferation and in vivo tumorigenicity.

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Acknowledgements

We thank the Washington University Genome Sequencing Center for generating the high-quality sequence that facilitated the identification of ST7; S. Hoogstraten-Miller for assistance in the animal studies; and B. Vogelstein, F. Collins, P. Meltzer, A. Baxevanis, J. Thomas and L. Everett for critical review of the manuscript.

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Authors and Affiliations

  1. Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA

    Jean C. Zenklusen & Eric D. Green

  2. Department of Carcinogenesis, M.D. Anderson Cancer Center, The University of Texas, Smithville, Texas, USA

    Claudio J. Conti

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  1. Jean C. Zenklusen
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Correspondence to Jean C. Zenklusen or Eric D. Green.

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Zenklusen, J., Conti, C. & Green, E. Mutational and functional analyses reveal that ST7 is a highly conserved tumor-suppressor gene on human chromosome 7q31. Nat Genet 27, 392–398 (2001). https://doi.org/10.1038/86891

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