TERT promoter mutations and monoallelic activation of TERT in cancer
TERT promoter mutations and monoallelic activation of TERT in cancer
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DOI：
10.1038/oncsis.2015.39
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发表时间：
2015-12-01
期刊：
影响因子：
6.2
通讯作者：
Kryukov, G. V.
中科院分区：
文献类型：
--
作者：
Huang, F. W.;Bielski, C. M.;Kryukov, G. V.
在这里，我们报告，端粒酶（TERT）的启动子突变，在癌症中最常见的非编码突变，引起单等位基因表达的端粒酶。通过深度RNA测序，我们发现人类癌细胞系中的TERT激活可以以单等位基因或双等位基因的方式发生。毫无例外，热点TERT启动子突变导致仅一个等位基因的再表达，占所观察到的单等位基因TERT表达病例的大约一半。此外，我们发现单等位基因TERT表达在某些肿瘤类型中非常普遍，并且在广泛的癌症中广泛存在。总之，这些观察结果提供了对癌症中的TERT激活机制和非编码突变后果的见解。
Here we report that promoter mutations in telomerase (TERT), the most common noncoding mutations in cancer, give rise to monoallelic expression of TERT. Through deep RNA sequencing, we find that TERT activation in human cancer cell lines can occur in either mono-or biallelic manner. Without exception, hotspot TERT promoter mutations lead to the re-expression of only one allele, accounting for approximately half of the observed cases of monoallelic TERT expression. Furthermore, we show that monoallelic TERT expression is highly prevalent in certain tumor types and widespread across a broad spectrum of cancers. Taken together, these observations provide insights into the mechanisms of TERT activation and the ramifications of noncoding mutations in cancer.