Concordance for clonal hematopoiesis is limited in elderly twins.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
23 01 2020
23 01 2020
Historique:
received:
28
05
2019
accepted:
06
10
2019
pubmed:
8
11
2019
medline:
1
7
2020
entrez:
8
11
2019
Statut:
ppublish
Résumé
Although acquisition of leukemia-associated somatic mutations by 1 or more hematopoietic stem cells is inevitable with advancing age, its consequences are highly variable, ranging from clinically silent clonal hematopoiesis (CH) to leukemic progression. To investigate the influence of heritable factors on CH, we performed deep targeted sequencing of blood DNA from 52 monozygotic (MZ) and 27 dizygotic (DZ) twin pairs (aged 70-99 years). Using this highly sensitive approach, we identified CH (variant allele frequency ≥0.5%) in 62% of individuals. We did not observe higher concordance for CH within MZ twin pairs as compared with that within DZ twin pairs, or to that expected by chance. However, we did identify 2 MZ pairs in which both twins harbored identical rare somatic mutations, suggesting a shared cell of origin. Finally, in 3 MZ twin pairs harboring mutations in the same driver genes, serial blood samples taken 4 to 5 years apart showed substantial twin-to-twin variability in clonal trajectories. Our findings propose that the inherited genome does not exert a dominant influence on the behavior of adult CH and provide evidence that CH mutations may be acquired in utero.
Identifiants
pubmed: 31697828
pii: S0006-4971(20)62289-3
doi: 10.1182/blood.2019001807
pmc: PMC6978156
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
269-273Subventions
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R023131/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M004422/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C22324/A23015
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/14/5/30893
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT098051
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 by The American Society of Hematology.
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