Barreto D C, Gomez R S, Bale A E, Boson W L, De Marco L
Department of Clinics, Universidade Federal de Minas Gerais, Brazil.
J Dent Res. 2000 Jun;79(6):1418-22. doi: 10.1177/00220345000790061101.
An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigated three cases of sporadic odontogenic keratocysts and three other cases associated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the first to describe a somatic mutation of PTCH in sporadic odontogenic keratocysts as well as two novel mutations in cysts associated with NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.
牙源性角化囊肿（OKC）是颌骨的一种良性囊性病变，可散发出现或与痣样基底细胞癌综合征（NBCCS）相关。最近，NBCCS的基因被克隆出来，显示为果蝇节段极性基因Patched（PTCH）的人类同源物，PTCH是一种肿瘤抑制基因。PTCH基因编码一种跨膜蛋白，其作用与刺猬信号蛋白相反，控制包括牙齿在内的许多组织中的细胞命运、模式形成和生长。我们研究了3例散发的牙源性角化囊肿病例以及另外3例与NBCCS相关的病例，寻找PTCH基因的突变。非放射性单链构象多态性分析和PCR产物的直接测序显示，1例散发囊肿的外显子3中有5个碱基对（bp）的缺失（518delAAGCG），以及2例与NBCCS相关囊肿中的突变，1个无义突变（C2760A）和1个错义突变（G3499A）。本报告首次描述了散发牙源性角化囊肿中PTCH的体细胞突变以及与NBCCS相关囊肿中的2种新突变，表明一部分散发角化囊肿具有相似的发病机制。
