PTCH gene mutations in odontogenic keratocysts
PTCH gene mutations in odontogenic keratocysts
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DOI：
10.1177/00220345000790061101
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发表时间：
2000-06-01
影响因子：
7.6
通讯作者：
De Marco, L
中科院分区：
文献类型：
--
作者：
Barreto, DC;Gomez, RS;De Marco, L
牙源性角化囊肿（OKC）是颌骨的一种良性囊性病变，偶尔发生或与痣样基底细胞癌综合征（NBCCS）有关。最近，NBCCS的基因被克隆，并显示是人类同源的果蝇节极性基因Patched（PTCH），一种肿瘤抑制基因。PTCH基因编码一种跨膜蛋白，其作用与Hedgehog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、模式和生长。我们调查了三例散发性牙源性角化囊肿和另外三例与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和PCR产物直接测序显示，在一个散发性囊肿的外显子3（518delAAGCG）的5个碱基对（bp）的缺失，以及在两个囊肿与NBCCS，一个无义（C2760A）和错义（G3499A）的改变。这份报告是第一个描述PTCH的体细胞突变的散发性牙源性角化囊肿，以及两个新的突变与NBCCS相关的囊肿，表明一个类似的发病机制，在一个子集的散发性角化囊肿。
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.