title: Underestimated PTCH1 mutation rate in sporadic keratocystic odontogenic tumors.
abstract: OBJECTIVE
  Keratocystic odontogenic tumors (KCOTs) are benign cystic lesions of the jaws that occur sporadically in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). The protein patched homolog 1 gene (PTCH1) is associated with NBCCS development and tumor genesis associated with this syndrome. However, previous studies have revealed that more than 85% of syndromic KCOTs and less than 30% of sporadic KCOTs harbor PTCH1 mutations. The significantly lower PTCH1 mutation rates observed in sporadic KCOTs suggest that they serve a minor role in pathogenesis. We aimed to discern the importance of PTCH1 mutations in sporadic KCOTs.
  
  
  METHODS
  PTCH1 mutational analysis was performed with 19 new sporadic KCOT cases by direct sequencing of epithelial lining samples separated from fibrous capsules. Using this approach, we further reexamined 9 sporadic KCOTs that were previously reported to lack PTCH1 mutations by our group.
  
  
  RESULTS
  Nineteen PTCH1 mutations were detected in patient samples from 16/19 new cases (84%) all these mutations were absent in fibrous tissues and peripheral blood specimens from the same patients. We also identified four PTCH1 mutations in 3/9 patients (33%) that were previously undetected.
  
  
  CONCLUSIONS
  These data indicated that PTCH1 mutations occur in sporadic KCOTs at a higher rate than previously suspected, owing to the masking effects of the attached stromal tissues in the test samples. 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.
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Jiafei
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Sun
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xuefen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Shi
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address: moleculecf@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address: litiejun22@vip.sina.com.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
mesh_terms: D006801:Humans; D009154:Mutation; D009808:Odontogenic Tumors / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface
keywords: Keratocystic odontogenic tumors; Mutation; PTCH1