Genetic changes of hedgehog components in syndromic keratocystic odontogenic tumors

Objectives: The aim of this study was to investigate genetic changes of negative components of hedgehog signaling pathway, PTCH, PTCH2 and SUFU, in keratocystic odontogenic tumors (KCOTs) associated with Gorlin syndrome. Methods: 11 Gorlin syndrome patients with KCOTs were collected. Genomic DNA and DNA from the tissue fragments were extracted from peripheral blood samples and KCOT lesions for all cases, respectively. Germline mutation analysis on PTCH gene was performed by direct sequencing. Loss of heterozygosity (LOH) of PTCH, PTCH2 and SUFU was analyzed in syndromic KCOT lesions by amplifying the specific polymorphic microsatellite markers and electrophoresis. Results: 10 germline mutations of PTCH gene were revealed from 11 Gorlin syndrome patients. LOH of PTCH was identified in 6 of 11 cases. No LOH was observed in PTCH2 and SUFU genes. Conclusions: Syndromic KCOTs showing germline mutations and frequent LOH of PTCH gene supports the two-hit model for the tumorigenesis of KCOTs in Gorlin syndrome.