Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients
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DOI：
10.1016/j.ccell.2018.07.001
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发表时间：
2018-08-13
期刊：
影响因子：
50.3
通讯作者：
Ratsch, Gunnar
中科院分区：
文献类型：
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作者：
Kahles, Andre;Lehmann, Kjong-Van;Ratsch, Gunnar
我们对来自 8,705 名患者的 32 种癌症基因组图谱癌症类型的选择性剪接进行了全面分析，通过重新分析 RNA 和全外显子组测序数据来检测选择性剪接事件和肿瘤变异。肿瘤的选择性剪接事件比正常样本多出 30%。体细胞变体与选择性剪接事件的关联分析证实了已知的与 SF3B1 和 U2AF1 变体的反式关联，并鉴定了其他反式作用变体（例如，TADA1、PPP2R1A）。许多肿瘤具有数千个在正常样本中无法检测到的选择性剪接事件；平均而言，我们在 GTEx 正常人中不常见的肿瘤中鉴定出大约 930 个外显子-外显子连接（“新连接”）。根据临床蛋白质组学肿瘤分析联盟提供的乳腺癌和卵巢肿瘤样本数据，我们确认每个肿瘤样本有大约 1.7 个新连接和大约 0.6 个单核苷酸变异衍生肽，这些肽也被预测为主要组织相容性复合物-I 结合物（“推定新抗原”）。
Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified approximate to 930 exon-exon junctions ("neojunctions'') in tumors not typically found in GTEx normals. From Clinical Proteomic Tumor Analysis Consortium data available for breast and ovarian tumor samples, we confirmed approximate to 1.7 neojunction- and approximate to 0.6 single nucleotide variant-derived peptides per tumor sample that are also predicted major histocompatibility complex-I binders ("putative neoantigens'').