Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (<i>PTCH1)</i> and Suppressor of fused (<i>SUFU)</i><i>SUFU</i> mutation carriers appear to have an especially high risk of early-onset medulloblastoma.
A total of 8 single-nucleotide variants (SNVs) were detected in PTCH1, PTCH2 and SUFU in all the 5 subjects, however none of them was considered the pathogenic genetic mutation in this NBCCS family.
Basal cell naevus syndrome (BCNS) is an autosomal dominant disorder most commonly caused by a germline mutation in the Drosophila homologue of patched-1 gene (PTCH1).
We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome.
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene.
Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare, autosomal-dominant inherited genodermatosis linked to a mutation in the PTCH<sub>1</sub> (patched 1) gene and is characterized by a broad range of anomalies.
Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS).
Conversely, patients with PTCH1 germline mutations experience Shh overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) syndrome and an increased incidence of malignant transformation of CGNPs leading to medulloblastoma formation.
Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis.
The Hh signaling pathway is involved in the pathogenesis of several tumors, including nevoid basal cell carcinoma syndrome that is associated with an alteration of the patched-1 (PTCH1) gene.
The first link of Hh signaling to cancer was established through discovery of genetic mutations of Hh receptor gene PTCH1 being responsible for Gorlin syndrome in 1996.
Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations.
These results suggest that the PTCH1 gene plays a significant role in the pathogenesis of sporadic KCOTs, which is comparable to that observed in NBCCS patients.