文章：

急性白血病融合基因图谱：基于单中心连续1000例转录组测序揭示

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center

原文发布日期：2021-06-16

DOI: 10.1038/s41408-021-00504-5

类型: Article

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英文摘要：

Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.
 

摘要翻译： 

融合基因是急性白血病中重要的遗传异常，但其多样性和在急性白血病中的发生率仍有待系统描述。全转录组测序为分析融合基因提供了有力工具。本研究通过单中心连续1000例急性白血病病例（包括539例急性髓系白血病、437例急性淋巴细胞白血病和24例混合表型急性白血病患者）的全转录组测序数据，绘制了融合基因图谱。生物信息学分析共鉴定出792个高置信度框内融合事件（涉及296种独特融合），并将其分为四个等级。在整个队列中，61.8%的病例检出A级（致病性）、B级（可能致病性）和C级（意义未明）融合基因（急性髓系白血病为59.7%，急性淋巴细胞白血病为64.5%，混合表型急性白血病为63.6%）。分别有10.7%、48.5%和15.1%的病例检出涉及蛋白激酶基因、转录因子基因和表观遗传基因的融合基因。研究发现了大量新型融合基因（急性髓系白血病82种、B细胞急性淋巴细胞白血病88种、T细胞急性淋巴细胞白血病13种、混合表型急性白血病9种）。这份全面描绘的急性白血病融合基因真实图谱揭示了多个具有临床相关性且既往未被识别的融合基因。全转录组测序是一种有价值的工具，应广泛应用于急性白血病的常规诊断检测。

原文链接：

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center