Novel PTCH1 Gene Mutation in Nevoid Basal Cell Carcinoma Syndrome

Abstract

The purpose of this study was to report clinical characteristics, surgical results, and new PTCH1 gene mutations in nevoid basal cell carcinoma syndrome (NBCCS). Five patients were referred to the Department of Oral and Maxillofacial Surgery from local dental clinics between 2006 and 2016 to treat multiple keratocystic odontogenic tumors (KOTs). The cystic lesions were enucleated and peripheral ostectomy was performed to obtain safety margin. Recurrence and/or de novo development of KOT were assessed. Gene analysis using peripheral blood was performed in all patients to identify the mutation of PTCH1 gene. Three patients showed familial history of first-degree relatives. Of the major criteria, all patients presented KOT but only 1 patient had basal cell carcinoma. Of the minor criteria, 4 of the 5 patients presented macrocephaly and hypertelorism. During follow-up periods, all patients showed recurrence and/or de novo development of KOT in the jaw bone. Mutation analysis of PTCH1 gene showed 3 frameshifts (c.817_818ins(T), c.1226_1227ins(A), and c.2748del(C)), 1 splicing (c.1504-2A>T), and 1 missense (c.385T>C) mutation. Mutations were found in exon 1, 6, 9, 17, and intron 10. Regular follow-up is necessary because recurrence rate of KOT was very high. To help early diagnosis, it is essential to routinely perform genetic testing to detect PTCH1 gene mutations among patients with NBCCS.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations

“…Based on our previous studies, as well as reports from other groups, more than 80% of OKCs, both syndromic and sporadic, harbor PTCH1 mutations. 9 The results of 10 samples of OKCs with PTCH1 mutations as positive control was identical to previous result by our group. 28 In contrast, PTCH1 mutations were not detected in 14 OOCs by sequencing analysis using frozen specimens of the lining epithelium separated from the fibrous capsules.…”

“…Based on our previous studies, as well as reports from other groups, more than 80% of OKCs, both syndromic and sporadic, harbor PTCH1 mutations 9 . The results of 10 samples of OKCs with PTCH1 mutations as positive control was identical to previous result by our group 28 .…”

“…PTCH1 mutations may cause constitutive activation of SHH signaling, leading to aberrant and/or neoplastic growth. The ratio of PTCH1 mutation in syndromic OKC was over 80% 9 . However, this ratio in sporadic OKC was underestimated over the years 10 .…”

“…The ratio of PTCH1 mutation in syndromic OKC was over 80%. 9 However, this ratio in sporadic OKC was underestimated over the years. 10 The traditional protocol using the full thickness of the cyst wall (both lining epithelium and fibrous capsule) only detected 30% of sporadic OKCs harboring PTCH1 mutations.…”

Periocular Pigmented Basal Cell Carcinomas: Clinicopathologic Features and Mutational Profile

“…A range of tumor suppressor genes and proto-oncogenes have implicated in the pathogenesis of BCC, including the Hedgehog signaling components PTCH1 and SMO, TP53 (a tumor suppressor regulating the transition of the cell from G1 phase to S phase), and components of the RAS signaling cascade. 15 Consistent with findings reported in BCC, 9,[16][17][18][19] PTCH1 (14/31) and SMO (7/31) mutations were prevalent in our study population (Fig. 3C).…”