Clonal hematopoiesis before, during, and after human spaceflight Journal Article
| Authors: | Trinchant, N. M.; MacKay, M. J.; Chin, C.; Afshinnekoo, E.; Foox, J.; Meydan, C.; Butler, D.; Mozsary, C.; Vernice, N. A.; Darby, C.; Schatz, M. C.; Bailey, S. M.; Melnick, A. M.; Guzman, M.; Bolton, K.; Braunstein, L. Z.; Garrett-Bakelman, F.; Levine, R. L.; Hassane, D.; Mason, C. E. |
| Article Title: | Clonal hematopoiesis before, during, and after human spaceflight |
| Abstract: | Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing. We show CH with distinct mutational profiles and increasing allelic fraction that includes a high-risk, TET2 clone in one subject and two DNMT3A mutations on distinct alleles in the other twin. These astronauts exhibit CH almost two decades prior to the mean age at which it is typically detected and show larger shifts in clone size than age-matched controls or radiotherapy patients, based on a longitudinal cohort of 157 cancer patients. As such, longitudinal monitoring of CH may serve as an important metric for overall cancer and cardiovascular risk in astronauts. © 2020 The Author(s) Trinchant et al. examined twin astronauts for clonal hematopoiesis (CH). Some high-risk CH clones (TET2 and DNMT3A) were observed two decades before expected, with TET2 decreasing in spaceflight and elevating later post flight. Thus, CH is an important metric for overall cancer and cardiovascular risk in astronauts. © 2020 The Author(s) |
| Keywords: | radiation; tet2; dnmt3a; nasa; clonal hematopoiesis; chip; variant allele frequency; astronaut |
| Journal Title: | Cell Reports |
| Volume: | 33 |
| Issue: | 10 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2020-12-08 |
| Start Page: | 108458 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2020.108458 |
| PUBMED: | 33242405 |
| PROVIDER: | scopus |
| PMCID: | PMC9398182 |
| DOI/URL: | |
| Notes: | Article -- Erratum issued, see DOI: 10.1016/j.celrep.2021.108740 -- Export Date: 4 January 2021 -- Source: Scopus |
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