Hideshima Itsuki, Nakamura Yuriko, Onodera Shoko, Akashi Yoshihiko, Matsuzaka Kenichi, Takano Masayuki, Nomura Takeshi, Katakura Akira, Azuma Toshifumi
Department of Oral Pathobiological Science and Surgery, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
Department of Oral Oncology, Oral and Maxillofacial Surgery, Tokyo Dental College, Ichikawa, Chiba, Japan.
J Oral Pathol Med. 2025 Jan;54(1):12-21. doi: 10.1111/jop.13586. Epub 2024 Nov 24.
Odontogenic keratocyst (OKC) is a partial manifestation of Gorlin syndrome (GS), resulting from the abnormal activation of the hedgehog signaling pathway. OKC predominantly occurs in young adults and is mostly asymptomatic at the time of initial diagnosis. As OKC is asymptomatic, GS can be challenging to diagnose in certain instances. In this study, we attempted to identify asymptomatic GS from sporadic OKC cases using a previously developed gene panel for GS.
Genomic DNA was extracted from patient samples. These DNA samples were analyzed using the AmpliSeq Custom DNA Panel (Illumina), which was specifically designed to target four previously established genes (PTCH1, PTCH2, SMO, and SUFU). Mutations from patients were predicted using tools, such as MutationTaster, CADD, and Polyphen-2.
Thirty-one patients with OKC were included: 22 sporadic, 9 syndromic, 14 cases with dentigerous cysts, and 3 patients with orthokeratinized odontogenic cysts. One patient with sporadic OKC carried 50% genetic mutation in the cyst and blood, indicative of GS. PTCH1 mutations were found in one of the 14 patients with dentigerous cysts, 3 of the 17 first-time sporadic cases, and all four recurrent cases. Resected OKC tissues revealed a PTCH1 mutation.
We found one patient with GS from those diagnosed with sporadic OKC. Our findings suggest that PTCH1 mutations are associated with postoperative recurrence of OKC, implying that hedgehog-related gene variations may contribute to jaw cyst development and improve the prognosis of OKC.
牙源性角化囊肿（OKC）是戈林综合征（GS）的部分表现，由刺猬信号通路的异常激活引起。OKC主要发生于年轻人，初诊时大多无症状。由于OKC无症状，在某些情况下诊断GS具有挑战性。在本研究中，我们试图使用先前开发的GS基因检测板从散发性OKC病例中识别无症状的GS。
从患者样本中提取基因组DNA。使用AmpliSeq定制DNA检测板（Illumina）对这些DNA样本进行分析，该检测板专门针对四个先前确定的基因（PTCH1、PTCH2、SMO和SUFU）。使用MutationTaster、CADD和Polyphen-2等工具预测患者的突变。
纳入31例OKC患者：22例散发性、9例综合征性、14例含牙囊肿患者和3例正角化牙源性囊肿患者。1例散发性OKC患者的囊肿和血液中携带50%的基因突变，提示为GS。在14例含牙囊肿患者中的1例、17例初发散发性病例中的3例以及所有4例复发病例中发现了PTCH1突变。切除的OKC组织显示存在PTCH1突变。
我们在诊断为散发性OKC的患者中发现1例GS患者。我们的研究结果表明，PTCH1突变与OKC术后复发相关，这意味着刺猬相关基因变异可能与颌骨囊肿的发生有关，并可改善OKC的预后。
