Department of Oral Pathology, Peking University, School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing 100081, PR China.
Oral Oncol. 2009 Oct;45(10):861-5. doi: 10.1016/j.oraloncology.2009.02.003. Epub 2009 Apr 9.
Mutations in PTCH1 gene are responsible for majority of nevoid basal cell carcinoma syndrome (NBCCS) as well as for some related sporadic neoplasms. Odontogenic keratocysts (OKCs) are locally aggressive jaw lesions that may occur in isolation or in association with NBCCS. Mutations of PTCH1 would lead to constitutive activation of Sonic hedgehog (SHH) signaling pathway and result in aberrant cell proliferation. To clarify the role of PTCH1 in OKCs, mutational analysis was undertaken in eight sporadic and four NBCCS-associated OKCs and six PTCH1 mutations were identified in two sporadic and three NBCCS-associated cases. The epithelial cell proliferation as assessed by Ki67 labeling was studied in a total cohort of 62 OKCs (42 sporadic and 20 syndromic cases) with known PTCH1 status. The epithelial Ki67 labeling in OKCs with PTCH1 mutation was significantly higher than that in cases with no PTCH1 mutation. Furthermore, OKCs harboring PTCH1 truncation-causing mutations showed an even greater Ki67 labeling index than those with non-truncation-causing mutations. These results suggest that PTCH1 mutations, particularly those causing protein truncations, are associated with a subgroup of OKCs showing increased proliferative activity and thus may relate to a phenotype of higher recurrent tendency.
PTCH1 基因突变负责大多数神经嵴基底细胞痣综合征（NBCCS）以及一些相关的散发性肿瘤。牙源性角化囊肿（OKCs）是局部侵袭性颌骨病变，可能单独发生或与 NBCCS 相关。PTCH1 的突变会导致 Sonic hedgehog（SHH）信号通路的组成性激活，并导致异常的细胞增殖。为了阐明 PTCH1 在 OKCs 中的作用，对 8 例散发性和 4 例 NBCCS 相关 OKCs 进行了突变分析，并在 2 例散发性和 3 例 NBCCS 相关病例中发现了 6 个 PTCH1 突变。通过 Ki67 标记评估了已知 PTCH1 状态的 62 例 OKCs（42 例散发性和 20 例综合征性病例）中的上皮细胞增殖情况。具有 PTCH1 突变的 OKCs 的上皮 Ki67 标记明显高于没有 PTCH1 突变的病例。此外，携带 PTCH1 截断突变的 OKCs 的 Ki67 标记指数甚至高于非截断突变的 OKCs。这些结果表明，PTCH1 突变，特别是导致蛋白截断的突变，与具有更高增殖活性的 OKCs 亚群相关，因此可能与更高复发倾向的表型有关。
