Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of gorlin syndrome

ABSTRACT Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities

of the skeleton and a predisposition to benign and malignant tumors1,2. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched

(_ptc_)3,4. Here we report that mice heterozygous for ptc develop many of the features characteristic of Corlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS),

the most common soft-tissue sarcoma in children5. The downstream signalling partner of _ptc, glil_, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the

_ptc-glil_ pathway may be common for the various tumors6,7 associated with the syndrome. _igf2_, implicated in the formation of RMSs8, was also overexpressed, suggesting cross-talk between

the _ptc_ and _igf2_ pathways in tumorigenesis. Developemental defects in Corlin syndrome resemble those induced by ionizing radiation9. We show that ptc heterozygous mice exhibit increased

incidence of radiation-induced teratogenesis. This suggests a role for _ptc_ in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic

(cancer) abnormalities observed in Gorlin syndrome. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CHARACTERIZATION OF A RHABDOMYOSARCOMA REVEALS A CRITICAL ROLE FOR SMG7 IN

CANCER CELL VIABILITY AND TUMOR GROWTH Article Open access 22 June 2023 HAPLOINSUFFICIENCY OF THE LYSOSOMAL SIALIDASE _NEU1_ RESULTS IN A MODEL OF PLEOMORPHIC RHABDOMYOSARCOMA IN MICE

Article Open access 20 September 2022 SYNTHETIC ESSENTIALITY BETWEEN PTEN AND CORE DEPENDENCY FACTOR PAX7 DICTATES RHABDOMYOSARCOMA IDENTITY Article Open access 17 September 2021 REFERENCES

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1034–1046 (1997). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Section on Genetics, National Institute of Mental Health, 36 Convent Drive,

Room 3006, Bethesda, MD, 20892, USA Heidi Hahn, Leszek Wojnowski, Anne M. Zimmer, Jennifer Hall & Andreas Zimmer * Veterinary Resources Program, National Institute for Research

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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hahn, H., Wojnowski, L., Zimmer, A. _et al._ Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. _Nat

Med_ 4, 619–622 (1998). https://doi.org/10.1038/nm0598-619 Download citation * Received: 27 February 1998 * Accepted: 23 March 1998 * Issue Date: 01 May 1998 * DOI:

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