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Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma

Abstract

A mutational analysis of the matrix metalloproteinase (MMP) gene family in human melanoma identified somatic mutations in 23% of melanomas. Five mutations in one of the most commonly mutated genes, MMP8, reduced MMP enzyme activity. Expression of wild-type but not mutant MMP8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression.

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Figure 1: Effects of MMP8 mutations on enzymic activity, growth on soft agar and growth in vivo.

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Acknowledgements

We thank M. Xu, J. Polite, I. Cardenas-Navia, D. Leja and I. Ginty for technical assistance. We thank R. Weinberg (Massachusetts Institute of Technology) for the Mel-STR cells, and W. Gahl (National Institutes of Health) and R. Alani (Johns Hopkins University) for normal melanocyte RNA. We also thank L. Matrisian, P. Meltzer, T. Waldman, G. Merlino, T. Hornyak and T. Bugge for their comments on the manuscript. Funded by the National Human Genome Research Institute and National Institute on Aging.

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Authors

Contributions

L.H.P. and Y.S. designed the study; J.R.W., P.F., A.C.F. and S.A.R. collected and analyzed the melanoma samples, A.S.B., J.C.C., N.S.A., P.B., P.P.-G., S.D., C.W., C.E.B., J.C.L. and Y.S. analyzed the genetic data; L.H.P., T.D.P., X.W., W.W., S.H.-M., A.A.M., M.P.O., J.D.H. and A.T.W. performed and analyzed the functional data. All authors contributed to the final version of the paper.

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Correspondence to Yardena Samuels.

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Supplementary Figures 1–7, Supplementary Tables 1–4, Supplementary Methods and Supplementary Note (PDF 560 kb)

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Palavalli, L., Prickett, T., Wunderlich, J. et al. Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat Genet 41, 518–520 (2009). https://doi.org/10.1038/ng.340

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