Genetic basis of calcifying cystic odontogenic tumors.
Genetic basis of calcifying cystic odontogenic tumors.
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DOI：
10.1371/journal.pone.0180224
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sakamoto K
中科院分区：
文献类型：
--
作者：
Yukimori A;Oikawa Y;Morita KI;Nguyen CTK;Harada H;Yamaguchi S;Kayamori K;Yamaguchi A;Ikeda T;Sakamoto K
钙化性牙源性囊性肿瘤是一种良性囊性肿瘤，可形成异常角化的影细胞。编码β-连环蛋白的CTNNB 1的突变与这些肿瘤的发生有关，但因果关系尚未确定。因此，在11个CCOT样本中通过靶向下一代测序检查了50个癌症基因中的突变热点。在11例病例中，有10例观察到CTNNB 1突变，但其他基因未发生突变。这些突变通过消除磷酸化位点Asp 32、Ser 33或Ser 37组成性地激活β-连环蛋白信号传导，并且与毛母质瘤和造釉细胞瘤性颅咽管瘤中报道的那些相似。相反，BRAF或NRAS突变分别在12例成釉细胞瘤和2例对照样本中观察到。在HEK 293细胞中，突变的CTNNB 1的过表达也上调了毛角蛋白，一种鬼细胞的标志物。此外，在两例BRAF和CTNNB 1突变的成釉细胞瘤中存在鬼细胞，表明鬼细胞是由于CTNNB 1突变而形成的。这些数据表明，CTNNB 1的突变是CCOT的主要驱动突变，CCOT是牙源性组织中毛母质瘤和造釉细胞瘤性颅咽管瘤的遗传类似物。
Calcifying cystic odontogenic tumors (CCOTs) are benign cystic tumors that form abnormally keratinized ghost cells. Mutations in CTNNB1, which encodes beta-catenin, have been implicated in the development of these tumors, but a causal relationship has not been definitively established. Thus, mutational hot spots in 50 cancer genes were examined by targeted next-generation sequencing in 11 samples of CCOT. Mutations in CTNNB1, but not in other genes, were observed in 10 of 11 cases. These mutations constitutively activate beta-catenin signaling by abolishing the phosphorylation sites Asp32, Ser33, or Ser37, and are similar to those reported in pilomatrixoma and adamantinomatous craniopharyngioma. In contrast, BRAF or NRAS mutations were observed in 12 and two control samples of ameloblastoma, respectively. In HEK293 cells, overexpression of mutated CTNNB1 also upregulated hair keratin, a marker of ghost cells. Furthermore, ghost cells were present in two cases of ameloblastoma with BRAF and CTNNB1 mutations, indicating that ghost cells form due to mutations in CTNNB1. The data suggest that mutations in CTNNB1 are the major driver mutations of CCOT, and that CCOT is the genetic analog of pilomatrixoma and adamantinomatous craniopharyngioma in odontogenic tissue.