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Background.  The pathogenesis underlying the increased predisposition to the development of basal cell carcinomas (BCCs) in the context of Gorlin-Goltz syndrome is linked to molecular mechanisms that differ from sporadic BCCs. Patients with Gorlin syndrome tend to develop multiple BCCs at an early age and present with tumors of non-sun-exposed skin. The aim of this study was to compare the proteomic profile of cultured fibroblast and fibroblast conditioned culture media of  PTCH1+  and nonmutated fibroblasts.  Results.  Proteomic analysis was performed using Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry in  PTCH1+  fibroblast conditioned media isolated from not affected sun-protected skin areas of Gorlin patients and from healthy subjects. 12 protein cluster peaks, >5 kDa, had significant differences in their peak intensities between  PTCH1+  and  PTCH1 − subject groups. We detected a strongly MMP1 overexpression in  PTCH1+  fibroblasts obtained from NBCCS patients with respect to healthy donors.  Conclusion.  Protein profiles in the fibroblast conditioned media revealed statistically significant differences between two different types (missense versus nonsense) of  PTCH1  mutations. These differences could be useful as signatures to identify  PTCH1  gene carriers at high risk for the development of NBCCS-associated malignancies and to develop novel experimental molecular tailored therapies based on these druggable targets.

biomed research international

Proteomic Analysis of<i>PTCH1</i>+/− Fibroblast Lysate and Conditioned Culture Media Isolated from the Skin of Healthy Subjects and Nevoid Basal Cell Carcinoma Syndrome Patients

Proteomic Analysis ofPTCH1+/− Fibroblast Lysate and Conditioned Culture Media Isolated from the Skin of Healthy Subjects and Nevoid Basal Cell Carcinoma Syndrome Patients