Abstract
Only a small proportion of cancers result from familial cancer syndromes with Mendelian inheritance. Nonfamilial, 'sporadic' cancers, which represent most cancer cases, also have a significant hereditary component1,2, but the genes involved have low penetrance and are extremely difficult to detect2,3. Therefore, mapping and cloning of quantitative trait loci (QTLs) for cancer susceptibility in animals could help identify homologous genes in humans. Several cancer-susceptibility QTLs have been mapped in mice and rats4,5, but none have been cloned so far. Here we report the positional cloning of the mouse gene Scc1 (Susceptibility to colon cancer 1)6 and the identification of Ptprj, encoding a receptor-type protein tyrosine phosphatase, as the underlying gene. In human colon, lung and breast cancers, we show frequent deletion of PTPRJ, allelic imbalance in loss of heterozygosity (LOH) and missense mutations. Our data suggest that PTPRJ is relevant to the development of several different human cancers.
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Acknowledgements
The authors thank V. Theodorou, E. Dijsselbloem, E. Anthony and M. Treur for technical assistance; J. de Moes, E. Delzenne-Goette and M. Timpico for help with breeding, tumor induction and autopsies; A. Berns, M. Snoek, J. Jonkers, H. Mikkers and A. Cleton-Jansen for helpful comments on the manuscript; E. Robanus for the human BAC filters; R. Pruntel for all the ABI runs; and S. Banus and H. van Kranen for their help with pyrosequencing. This work was supported by grants from the Dutch Cancer Society and the Dutch Basic Research Organization.
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Ruivenkamp, C., van Wezel, T., Zanon, C. et al. Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet 31, 295–300 (2002). https://doi.org/10.1038/ng903
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DOI: https://doi.org/10.1038/ng903
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