PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts
PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts
复制标题
在散发性牙源性角化囊肿中，PTCH1 改变很常见，但其他基因改变很少见
DOI：
10.1111/odi.13135
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发表时间：
2019
期刊：
影响因子：
3.8
通讯作者：
Li Tiejun
中科院分区：
文献类型：
--
作者：
Qu Jiafei;Zhang Jianyun;Zhang Heyu;Li Xuefen;Hong Yingying;Zhai Jiemei;Wang Yanjin;Chen Feng;Li Tiejun
目的牙源性角化囊肿(OKCs)是颌骨良性病变，具有较高的生长潜能和复发倾向。我们先前的研究表明，在散发性OKC中经常检测到的PTCH1突变可能被低估了，因为被测试组织中的间质成分的掩蔽作用。我们的目的是在更大范围内证实这些结果，并进一步对散发性OKC的基因组基础提出公正的看法。材料和方法我们分析了另外19例样本中的PTCH1突变。利用全外显子测序(WES)技术，我们进一步研究了5例散发性OKC中PTCH1缺失和杂合性缺失(LOH)的突变情况。结果结合我们之前报道的19例病例，30例(79%)存在PTCH1突变。通过全外显子测序和综合分析，在5个PTCH1阴性样本中确认了22个新突变。在WES样本和10例OKC的验证队列中未发现复发突变。结论我们的数据进一步证实了散发性OKC中存在频繁的PTCH1突变和其他罕见的基因改变，突显了SHH信号通路的中心作用。在PTCH1阴性的病例中，散布在OKC子集中的其他罕见突变与SHH途径无关。这些结果表明，SHH抑制剂可能对大多数OKC有效。
ObjectiveOdontogenic keratocysts (OKCs) are benign jaw lesions with high growth potential and propensity for recurrence. Our previous study revealed thatPTCH1mutations, which were frequently detected in sporadic OKCs, might be underestimated due to the masking effect of the stromal components within the tested tissues. We aimed to confirm these results in larger scale and further present the unbiased view of the genomic basis of sporadic OKCs exceptPTCH1.Materials and methodsWe analyzedPTCH1mutations in additional 19 samples. Using whole‐exome sequencing (WES), we further characterized the mutational landscape of five sporadic OKC samples lackingPTCH1mutation and loss of heterozygosity (LOH).ResultsCombined with our previously reported 19 cases, thirty of 38 (79%) cases harboredPTCH1mutations. Through whole‐exome sequencing and integrative analysis, 22 novel mutations were confirmed among fivePTCH1‐negative samples. No recurrent mutations were identified in the WES samples and validation cohort of 10 OKCs.ConclusionsOur data further confirmed the frequentPTCH1mutation and other rare genetic alterations in sporadic OKCs, highlighting the central role of SHH signaling pathway. InPTCH1‐negative cases, other rare mutations scattered in a subset of OKCs were independent of the SHH pathway. These results suggested that an SHH inhibitor may be effective to treat the majority of OKCs.