engleski

Patched in development malformations and cancer. Alterations of Patched in ovarian fibromas and non inflammatory cysts

Constitutional hemizygous inactivation of PTCH, the Shh/Ptch signaling pathway gene, which moderates Shh signalling, manifests itself as Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a condition variably characterized by developmental disorders and malformations, and by predisposition to certain malignancies. The PTCH gene, a human homologue of the Drosophila segment polarity gene patched, maps to chromosome 9q22.3 and loss of heterozygosity (LOH) at this site in both sporadic and hereditary basal cell carcinomas, meduloblastomas and ovarian fibromas suggests that it functions as a tumor suppressor. We used DNA from fresh tissues and blood leukocytes, which were typed for several short tandem repeat polymorphism's at 9q21-q31, and SSCP of PTCH exons, analyzing variability in PTCH exons. PCR reactions were performed and products were fractionated on 5 - 8 % polyacrylamide gels. We found LOH in sporadic basocellular carcinomas in more than 70 % of cases and in 30 % of ovarian fibromas. So far we detected in more than 60 % of cases that the cyst lining of jaws loses the normal copy of the PTCH while retaining the mutant copy. Our studies of LOH in sporadic ovarian fibromas and noninflammatory cysts, and aberrant SSCP pattern for PTCH exons, contribute to the ptch role in their genesis. More generally, PTCH alterations may prove to be a necessary, and perhaps the initiating event, in formation and growth of various noninflammatory cysts, especially with our observations of incomplete heterozygosity which we interpreted as LOH in this region for ovarian dermoid cysts. This would be consistent with our view that local PTCH inactivation can, under predisposing circumstances, lead to persistent though not by itself truly aggressive cell proliferation.

signaling; Patched; development; cancer

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