title: Proteomic analysis of PTCH1+/- fibroblast lysate and conditioned culture media isolated from the skin of healthy subjects and nevoid basal cell carcinoma syndrome patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Bertazzoni
authors.affiliation: Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, 16132 Genoa, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Monari
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Cuoghi
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bergamini
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bellei
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benassi
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Azzoni
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Petrachi
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Magnoni
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.affiliation: Department of Plastic and Reconstructive Surgery, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Loschi
authors.affiliation: Department of Neurosciences, University of Padua, 35100 Padua, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pollio
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, 41100 Modena, Italy.
authors.forename: Alexander Michael
authors.initials: AM
authors.lastname: Witkowski
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Via del Pozzo, 41100 Modena, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Tomasi
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000032:analysis / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D040901:Proteomics; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface