The genomic landscape of nasopharyngeal carcinoma
The genomic landscape of nasopharyngeal carcinoma
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DOI：
10.1038/ng.3006
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发表时间：
2014-08-01
期刊：
影响因子：
30.8
通讯作者：
Koeffler, H. Phillip
中科院分区：
文献类型：
--
作者：
Lin, De-Chen;Meng, Xuan;Koeffler, H. Phillip
鼻咽癌(NPC)具有极不对称的种族和地理分布，在基因水平上缺乏了解，需要有效的治疗方法。在这里，我们使用全外显子组和靶向深度测序以及SNP阵列分析来确定128例鼻咽癌患者的突变情况。这些方法揭示了一个明显的突变特征和9个显著突变的基因，其中许多以前没有涉及到鼻咽癌。值得注意的是，综合分析显示，影响几个重要细胞过程和途径的遗传损伤丰富，包括染色质修饰、ERBB-PI3K信号和自噬机制。进一步的功能研究表明，这些病变与鼻咽癌恶性表型的生物学相关性。此外，我们还发现了一些新的可用药候选药物，因为它们的基因组发生了变化。总之，我们的研究为全面了解和探索鼻咽癌的新疗法提供了分子基础。
Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.