Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts.
Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts.
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DOI：
10.1038/s42003-022-03777-z
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发表时间：
2022-08-17
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
随着计划中的深空和商业太空飞行，在解决宇航员的健康风险方面仍然存在差距。多项研究表明，造血细胞克隆性增殖与血液系统恶性肿瘤和心脏代谢性疾病之间存在关联。这种在没有明显造血障碍的情况下克隆的扩张被称为不确定潜能的克隆性造血(CHIP)。使用深度、纠错、定向DNA测序，我们分析了从1998-2001年间执行航天飞机任务的14名宇航员采集的去身份血液样本中分离的外周血单核细胞中CH-DRIVER基因的体细胞突变。我们在17个CH-DRIVER基因中发现了34个变异等位基因比例相对较低的非同义突变，其中最常见的突变是TP53和DNMT3A。在相对年轻的宇航员队列的血液中存在这些小克隆，这就需要对它们的临床相关性和在监测宇航员健康方面的潜在应用进行进一步的回顾和前瞻性调查。从1998-2001年间执行航天飞机飞行任务的14名宇航员的血液样本中分离出的外周血单核细胞的深度靶向DNA测序发现了34个非沉默突变，主要是在TP53和DNMT3A中。
With planned deep space and commercial spaceflights, gaps remain to address health risks in astronauts. Multiple studies have shown associations between clonal expansion of hematopoietic cells with hematopoietic malignancies and cardiometabolic disease. This expansion of clones in the absence of overt hematopoietic disorders is termed clonal hematopoiesis (CH) of indeterminate potential (CHIP). Using deep, error-corrected, targeted DNA sequencing we assayed for somatic mutations in CH-driver genes in peripheral blood mononuclear cells isolated from de-identified blood samples collected from 14 astronauts who flew Shuttle missions between 1998–2001. We identified 34 nonsynonymous mutations of relatively low variant allele fraction in 17 CH-driver genes, with the most prevalent mutations in TP53 and DNMT3A. The presence of these small clones in the blood of relatively young astronaut cohort warrants further retrospective and prospective investigation of their clinical relevance and potential application in monitoring astronaut’s health. Deep targeted DNA sequencing of peripheral blood mononuclear cells isolated from blood samples from 14 astronauts who flew Shuttle missions between 1998–2001 identifies 34 non-silent mutations, predominantly in TP53 and DNMT3A.
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影响因子：
4.7
作者：
Kurzer JH;Weinberg OK
通讯作者：
Weinberg OK
影响因子：
30.8
作者：
Makishima H;Yoshizato T;Yoshida K;Sekeres MA;Radivoyevitch T;Suzuki H;Przychodzen B;Nagata Y;Meggendorfer M;Sanada M;Okuno Y;Hirsch C;Kuzmanovic T;Sato Y;Sato-Otsubo A;LaFramboise T;Hosono N;Shiraishi Y;Chiba K;Haferlach C;Kern W;Tanaka H;Shiozawa Y;Gómez-Seguí I;Husseinzadeh HD;Thota S;Guinta KM;Dienes B;Nakamaki T;Miyawaki S;Saunthararajah Y;Chiba S;Miyano S;Shih LY;Haferlach T;Ogawa S;Maciejewski JP
通讯作者：
Maciejewski JP
影响因子：
8
作者：
Sano S;Wang Y;Ogawa H;Horitani K;Sano M;Polizio AH;Kour A;Yura Y;Doviak H;Walsh K
通讯作者：
Walsh K
影响因子：
3.4
作者：
Chylack, Leo T., Jr.;Peterson, Leif E.;Cucinotta, Francis A.
通讯作者：
Cucinotta, Francis A.
影响因子：
12.8
作者：
Muendlein, Axel;Kinz, Elena;Lang, Alois H.
通讯作者：
Lang, Alois H.