Underestimated PTCH1 mutation rate in sporadic keratocystic odontogenic tumors

作者：Qu, Jiafei; Yu, Feiyan; Hong, Yingying; Guo, Yanyan; Sun, Lisha; Li, Xuefen; Zhang, Jianyun; Zhang, Heyu; Shi, Ruirui; Chen, Feng^*; Li, Tiejun

来源：Oral Oncology, 2015, 51(1): 40-45.

DOI：10.1016/j.oraloncology.2014.09.016

• PTCH1
• Mutation
• Keratocystic odontogenic tumors

Objectives: 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. @@@ Materials and 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. @@@ Discussion: 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.

• 出版日期2015-1
• 单位北京大学