Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hahn, H. et al.

Hahn, Wojnowski, Specht, Kappler, Calzada-Wack, Potter, Zimmer, Müller, Samson, Quintanilla-Martinez, Zimmer,

Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children (Dagher, R., and Helman, L. (1999) Oncologist 4, 34-44), whereas medulloblastoma, a highly malignant tumor of the cerebellum, accounts for 20% of childhood brain tumors (Goodrich, L. V., and Scott, M. P. (1998) Neuron 21, 1243-1257). Both tumors are associated with a deficiency in the tumor suppressor Patched (PTCH) in Gorlin syndrome (Gorlin, R. J. (1987) Medicine (Baltimore) 66, 98-113), and they are present in the corresponding murine models. RMS in Ptch mutant mice consistently contain elevated levels of the tumor growth- promoting insulin-like growth factor 2 (Igf2). We have investigated the mechanism of Igf2 overexpression and its significance in medulloblastoma and RMS tumorigenesis. Here we report that Igf2 is indispensable for the formation of medulloblastoma and RMS in Ptch mutants. Overexpression of Igf2 in RMS in these mice does not involve loss of imprinting, uniparental disomy, amplification of the Igf2 locus, or polyploidy. Since Igf2 is also overexpressed in non-tumor tissue deficient in Ptch, these observations suggest that Ptch regulates Igf2 levels through a transcriptional mechanism. They also identify Igf2 as a potential target for medulloblastoma and RMS.[1]

References

Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. Hahn, H., Wojnowski, L., Specht, K., Kappler, R., Calzada-Wack, J., Potter, D., Zimmer, A., Müller, U., Samson, E., Quintanilla-Martinez, L., Zimmer, A. J. Biol. Chem. (2000) [Pubmed]

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