Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types.
Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types.
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DOI：
10.1016/j.celrep.2018.01.088
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发表时间：
2018-04-03
期刊：
影响因子：
8.8
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Seiler M;Peng S;Agrawal AA;Palacino J;Teng T;Zhu P;Smith PG;Cancer Genome Atlas Research Network;Buonamici S;Yu L
最近，剪接因子基因的热点突变在血液系统恶性肿瘤中被报道的频率很高，这表明了RNA剪接在癌症中的重要性。我们分析了《癌症基因组图谱》(TCGA)中33种肿瘤类型的全外显子测序数据，发现119个剪接因子基因具有显著的非沉默突变模式，包括突变过度表达、反复功能丧失(肿瘤抑制子样)或热点突变(癌基因样)。此外，RNA测序分析揭示了与选定的剪接因子突变相关的剪接事件的改变。此外，我们能够识别与这些突变的存在相关的常见基因途径谱。我们的分析表明，参与RNA剪接过程的基因的体细胞变化在癌症中很常见，可能代表了肿瘤发生的一个被低估的标志。简而言之：塞勒等人。据报道，在TCGA中，有119个剪接因子基因携带33种肿瘤类型的推定驱动突变。最常见的突变似乎是相互排斥的，并与谱系无关的改变剪接有关。带有这些突变的样本显示细胞自主途径的放松调控和免疫渗透。
Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. In Brief: Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration.
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