title: Molecular pathogenesis of keratocystic odontogenic tumors developing in nevoid basal cell carcinoma syndrome.
abstract: OBJECTIVE
  The aim of this study was to investigate the molecular pathogenesis of keratocystic odontogenic tumors (KCOTs) that developed in nevoid basal cell carcinoma syndrome (NBCCS) patients.
  
  
  METHODS
  We analyzed germline and somatic mutations of the PTCH1 and its related genes, SMO and SUFU in 10 KCOTs that developed in 8 unrelated NBCCS patients. Methylation status of the PTCH1 promoter was also investigated by bisulfite sequencing.
  
  
  RESULTS
  Somatic mutations of PTCH1 were detected in 3 KCOTs. Two out of 3 somatic mutations were either identified as a polymorphism or located on the same allele as the germline mutation. Neither abnormal methylation of the PTCH1 promoter, loss of PTCH1, nor somatic mutation of SMO or SUFU was detected in any of the samples.
  
  
  CONCLUSIONS
  Our results suggest that the tumorigenesis of most KCOTs associated with NBCCS cannot be explained by the classical 2-hit theory.
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors: Maiko
authors: M
authors: Suzuki
authors: Kazuaki
authors: K
authors: Nagao
authors: Hiromi
authors: H
authors: Hatsuse
authors: Ryo
authors: R
authors: Sasaki
authors: Kayoko
authors: K
authors: Saito
authors: Katsunori
authors: K
authors: Fujii
authors: Toshiyuki
authors: T
authors: Miyashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001478:Basal Cell Nevus Syndrome / Q000150:complications* / Q000235:genetics; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009808:Odontogenic Tumors / Q000150:complications* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface