Clonal Hematopoiesis Before, During, and After Human Spaceflight.

Mencia-Trinchant, Nuria, MacKay, Matthew J, Chin, Christopher, Afshinnekoo, Ebrahim, Foox, Jonathan, Meydan, Cem, Butler, Daniel, Mozsary, Christopher, Vernice, Nicholas A, Darby, Charlotte, Schatz, Michael C, Bailey, Susan M, Melnick, Ari M, Guzman, Monica L, Bolton, Kelly, Braunstein, Lior Z, Garrett-Bakelman, Francine, Levine, Ross L, Hassane, Duane C, Mason, Christopher E (December 2020) Clonal Hematopoiesis Before, During, and After Human Spaceflight. Cell Reports, 33 (10). p. 108458. ISSN 2211-1247

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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.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > neoplasms bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell types > hematopoietic cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > hematopoietic cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > hematopoietic cell organism description > animal > mammal > primates > hominids organism description > animal > mammal > primates > hominids > human organism description > animal > mammal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > methyltransferase organism description > animal > mammal > primates bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Schatz, Michael C.
Communities:	CSHL labs > Schatz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	8 December 2020
Date Deposited:	07 May 2021 18:35
Last Modified:	21 Nov 2024 19:04
PMCID:	PMC9398182
URI:	https://repository.cshl.edu/id/eprint/40056

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