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Stops along the RAS pathway in human genetic disease

Nature Medicine volume 12, pages 283–285 (2006)Cite this article

Mutations in components of the RAS-MAPK pathway provide a unifying mechanism for several phenotypically overlapping, yet clinically distinct human 'neuro-cardio-facial-cutaneous' (NCFC) syndromes. These rare diseases may provide new insights into the regulation of this pathway and its role in various cancers.

Physicians have long recognized significant phenotypic overlap between the genetic disorders neurofibromatosis Type I (NF1), Noonan syndrome, LEOPARD syndrome, cardio-facio-cutaneous (CFC) syndrome and Costello syndrome. Yet because these syndromes can usually be distinguished clinically, it has been unclear whether their common features reflect a similar underlying pathogenesis. Now, recent studies show that each is caused by germline mutations in key components of the highly conserved RAS-RAF-ERK-MAP-kinase cascade, better known for its roles in growth factor and cytokine signaling and cancer pathogenesis.

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Figure 1: Molecular basis of the neuro-cardio-facial-cutaneous (NCFC) syndromes.

Katie Ris

References

  1. Cichowski, K. & Jacks, T. Cell 104, 593–604 (2001).

    CAS  Article  Google Scholar 

  2. Tartaglia, M. & Gelb, B.D. Annu. Rev. Genomics Hum. Genet. 6, 45–68 (2005).

    CAS  Article  Google Scholar 

  3. Aoki, Y. et al. Nat. Genet. 37, 1038–1040 (2005).

    CAS  Article  Google Scholar 

  4. Rodriguez-Viciana, P. et al. Science published online 26 January 2006 (10.1126/science.1124642).

  5. Niihori, T. et al. Nat. Genet. 38, 294–296 (2006).

    CAS  Article  Google Scholar 

  6. Schubbert, S. et al. Nat. Genet. 38, 331–336 (2006).

    CAS  Article  Google Scholar 

  7. Kolch, W. Nat. Rev. Mol. Cell. Biol. 6, 827–837 (2005).

    CAS  Article  Google Scholar 

  8. Keilhack, H., David, F.S., McGregor, M., Cantley, L.C. & Neel, B.G. J. Biol. Chem. 280, 30984–30993 (2005).

    CAS  Article  Google Scholar 

  9. Wan, P. T. et al. Cell 116, 855–867 (2004).

    CAS  Article  Google Scholar 

  10. Garnett, M. J., Rana, S., Paterson, H., Barford, D. & Marais, R. Mol. Cell 20, 963–969 (2005).

    CAS  Article  Google Scholar 

  11. Kontaridis, M.I., Swanson, K.D., David, F.S., Barford, D. & Neel, B.G. J. Biol. Chem. published online 25 December 2005 (10.1074/jbc.M513068200).

  12. Araki, T. et al. Nat. Med. 10, 849–857 (2004).

    CAS  Article  Google Scholar 

  13. Mor, A. & Philips, M.R. Annu. Rev. Immunol. published online 16 January 2006 (10.1146/annurev.immunol.24.021605.090723).

  14. Inoki, K., Corradetti, M.N. & Guan, K.L. Nat. Genet. 37, 19–24 (2005).

    CAS  Article  Google Scholar 

  15. Sebolt-Leopold, J.S. & Herrera, R. Nat. Rev. Cancer 4, 937–947 (2004).

    CAS  Article  Google Scholar 

  16. Solit, D.B. et al. Nature 439, 358–362 (2006).

    CAS  Article  Google Scholar 

Download references

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Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Cancer Biology Program, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Mohamed Bentires-Alj, Maria I Kontaridis & Benjamin G Neel

  2. Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrative Genoproteomics, University of Liège, Domaine du Sart-Tilman, 4000, Liège, Belgium

    Mohamed Bentires-Alj, Maria I Kontaridis & Benjamin G Neel

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  1. Mohamed Bentires-Alj
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  2. Maria I Kontaridis
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  3. Benjamin G Neel
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Bentires-Alj, M., Kontaridis, M. & Neel, B. Stops along the RAS pathway in human genetic disease. Nat Med 12, 283–285 (2006). https://doi.org/10.1038/nm0306-283

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