engleski

Role of SHH/PTCH/SMO signalling pathway in pathognesis of malignant schwanoma

Introduction: Schwanoma is tumor which derives from schwann cells, neuroglia that wrap around axons in nervous system forming the myelin sheath. Schwannoma is relatively rare tumor, it can derive from any cranial or peripheral nerve, but mostly they came from n. statoacusticus. The genetic basis of the schwanoma tumor is not known. During development Schwann cells secrete ligand Desert hedgehog, which bind to its receptor and can be detected in the mesenchyme. Desert Hedgehog and Sonic Hedgehog are ligands for glycoprotein Patched (Ptch), receptor which with cooreceptor Smo (Smoothened) transmit signal into nucleus. Ptch is located in membrane, has 12 transmembrane domains and two big extracellular loops between which ligand Hedgehog is placed. Ptch is member of the Hedgehog/Patched/Smoothened signalling pathway (or SHH/PTCH/SMO signalling pathway). We think that mutations in Patched might disturb signal transduction, which can contribute to development of schwanoma. Material and Methods: We report findings in one family with malignant schwanoma. At least two family members are affected. Results: We found allelic loss in 9q22.3 region (where PTCH is mapped) for three polymorphic markers D9S180, D9S287 and PTCH intra of one affected family member. Two of markers are in close vicinity of PTCH gene and intragenic marker PTCH intra is located in first intron of PTCH. Although we find allelic loss we didn't find mutation in coding regions of PTCH. In our next step we shall look for mutations in promoter region of Ptch and in expression profiles of all members of the pathway. Conclusions: We intend to answer if the loss of function of PTCH gene indicated through allelic loss can be confirmed either through mutations in promoter of PTCH or through impaired expression any of members of the SHH/PTCH/SMO pathway, or caused by innapropriate methylation of promoter regions.

schwanomma

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