Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts

Abstract

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.

Current Knowledge about the Impact of Microgravity on Gene Regulation

“…Deep space exploration needs further studies to predict astronauts’ health risks [ 132 ]. Applying deep, error-corrected, targeted DNA sequencing, Brojakowska et al [ 132 ] focused on somatic mutations in clonal hematopoiesis (CH)-driver genes in PBMC isolated from the de-identified blood samples of 14 Space Shuttle astronauts. They found 34 nonsynonymous mutations in 17 CH-driver genes, with the most prevalent mutations in TP53 and DNMT3A.…”

“…They found 34 nonsynonymous mutations in 17 CH-driver genes, with the most prevalent mutations in TP53 and DNMT3A. Therefore, future retrospective and prospective investigations of their clinical relevance are necessary [ 132 ].…”

Assessing the Nucleotide-Level Impact of Spaceflight Stress using RNA-Sequencing Data

“…The difference in the proportions of the other types of point mutations may have also been significant if the samples were in spaceflight for longer than five days. A study examined mutations accumulated in astronauts using DNA 11 . Even though they were only aboard the Space Station for a median of 12 days, a significant number of mutations was observed 11 .…”

“…A study examined mutations accumulated in astronauts using DNA 11 . Even though they were only aboard the Space Station for a median of 12 days, a significant number of mutations was observed 11 . In contrast to our study, they observed a higher number of transition mutations.…”

“…Damage was also observed in cells exposed for as little as nine days on the Space Shuttle 4 . Long-term space radiation exposure increases astronauts’ risk of cancer, cataracts, and neurological disorders 11,12 . In plants, spaceflight has demonstrated links to changed alternative splicing patterns, epigenetic patterns, and germination rates 7,13-15 .…”