Large-Scale Identification of Clonal Hematopoiesis and Mutations Recurrent in Blood Cancers.
Large-Scale Identification of Clonal Hematopoiesis and Mutations Recurrent in Blood Cancers.
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DOI：
10.1158/2643-3230.bcd-20-0094
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发表时间：
2021-05
影响因子：
11.2
通讯作者：
Mason CC
中科院分区：
文献类型：
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作者：
Feusier JE;Arunachalam S;Tashi T;Baker MJ;VanSant-Webb C;Ferdig A;Welm BE;Rodriguez-Flores JL;Ours C;Jorde LB;Prchal JT;Mason CC
克隆性造血潜能不确定(CHIP)的特征是在没有血液系统恶性肿瘤证据的人中检测到与造血相关的基因突变。我们试图通过对48项体细胞突变研究进行数据挖掘分析，确定可用于芯片检测的其他癌症呈现突变，这些研究报告了7,430名成人和儿童恶性血液病患者的突变。在提取了20,141个改变蛋白质的突变后，我们确定了434个显著的重复突变热点，其中364个发生在可以用于芯片评估的座位上。然后，我们对来自三个非癌症队列的4538人的整个外显子组测序数据进行了额外的大规模分析，以寻找克隆性突变。我们发现，CHIP突变与血癌突变热点报告的突变相同的队列综合患病率为1.8%，其中一些CHIP突变发生在儿童中。我们的发现可能有助于改善儿童和成人的芯片检测和癌症前监测。
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations useable for CHIP detection by performing a data mining analysis of 48 somatic mutation studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with hematologic malignancies. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole exome sequencing data from 4,538 persons belonging to three non-cancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and pre-cancer surveillance for both children and adults.