The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations
The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations
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DOI：
10.1182/blood-2014-05-576157
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发表时间：
2015-01-22
期刊：
影响因子：
20.3
通讯作者：
Riva, Laura
中科院分区：
文献类型：
--
作者：
Bodini, Margherita;Ronchini, Chiara;Riva, Laura
使用2种不同的生物信息学管道（SomaticSniper和MuTect）对来自133名急性髓性白血病（AML）患者的同一组基因组数据进行分析，在癌症基因组图谱项目中进行测序，得到了不一致的结果。我们随后在我们系列的20个白血病样本（19个原发性AML和1个继发性AML）上测试了这2个变体调用管道。通过验证许多预测的体细胞变体（变体等位基因频率范围从100%至5%），我们观察到显著不同的调用效率。特别是，尽管特异性相对较高，但两种管道的灵敏度均较差，导致假阴性率较高。我们的研究结果提出了这样一种可能性，即AML基因组的景观可能比以前报道的更复杂，其特征是存在数百个以低变异等位基因频率突变的基因，这表明基因组测序在临床上的应用需要仔细和严格的评估。我们认为，通过制定明确的实验和生物信息学指南，技术和工作流程标准化的改进是将下一代测序从研究应用到临床的基础，也是将基因组信息转化为更好的诊断和患者结局的基础。
The analyses carried out using 2 different bioinformatics pipelines (SomaticSniper and MuTect) on the same set of genomic data from 133 acute myeloid leukemia (AML) patients, sequenced inside the Cancer Genome Atlas project, gave discrepant results. We subsequently tested these 2 variant-calling pipelines on 20 leukemia samples from our series (19 primary AMLs and 1 secondary AML). By validating many of the predicted somatic variants (variant allele frequencies ranging from 100% to 5%), we observed significantly different calling efficiencies. In particular, despite relatively high specificity, sensitivity was poor in both pipelines resulting in a high rate of false negatives. Our findings raise the possibility that landscapes of AML genomes might be more complex than previously reported and characterized by the presence of hundreds of genes mutated at low variant allele frequency, suggesting that the application of genome sequencing to the clinic requires a careful and critical evaluation. We think that improvements in technology and workflow standardization, through the generation of clear experimental andbioinformatics guidelines, are fundamental to translate the use of next-generation sequencing from research to the clinic and to transform genomic information intobetter diagnosis and outcomes for the patient.