Keratocystic odontogenic tumors(KCOTs,previously known as odontogenic keratocysts) are aggressive,noninflammatory jaw lesions with a putative high growth potential and a propensity for recurrence.This article puts together a summary of the serial studies related to KCOTs undertaken by the author’s research group in recent years.Intraosseous jaw cysts with a solely orthokeratinized lining epithe-lium have been suggested to differ from the typical KCOTs.We report 20 cases of such cyst type under the term of ’orthokeratinized odontogenic cyst(OOC)’.Apart from the presence of a keratinizing epithelial lining,the OOC lacks the other histological features of KCOT,exhibits little if any tendency to recur,has no apparent association with NBCCS,may be cured by simple enucleation,and may thus constitute its own clinical entity.Mutations in PTCH1 gene are responsible for NBCCS and are related in tumors associated with this syndrome.We have so far detected 26 PTCH1 mutations(2 mutations occurred twice) in 10 out of 34(29.4%) sporadic and 14 out of 16(87.5%) NBCCS-associated KCOTs.The 26 mutations consisted of 10 frameshift,2 nonsense,3 aberrant splicing,4 in-frame insertion/deletion/ duplication and 7 missense mutations.Two missense mutations in PTCH2 were also detected in 2 out of 15 NBCCS related KCOT patients.By contrast,no pathogenic mutation was detected in SMO.Thus,our data,together with reports from ther groups,indicate that defects of PTCH1 are involved in the pathogenesis of syndromic as well as sporadic KCOTs.The pathogenic role of PTCH2 requires further investigation.A series of in vitro studies on bone resorption of KCOTs and ameloblastomas were undertaken by this group.The results indicate that odontogenic lesions could promote bone resorption in vitro and it is likely to be related to some of the cytokines secreted by the lesions.
Aim To clarify the role of PTCH in patients with NBCCS- related and non-sydromic keratocystic odontogenic tumors. Methodology Mutation analysis was undertaken in 8 sporadic and 4 NBCCS-associated KCOTs. Results Four novel and two known mutations were identifled in 2 sporadic and 3 syndromic cases, two of which being germline mutations （c.2179delT, c.2824delC） and 4 somatic mutations （c.3162dupG, c.1362-1374dup, c.1012 C〉T, c.403C〉T）. Conclusion Our findings suggest that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic KCOTs.
