Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis
Open accessAbstract
Aging is characterized by clonal expansion of myeloid-biased hematopoietic stem cells and by increased risk of myeloid malignancies. Exome sequencing of three elderly females with clonal hematopoiesis, demonstrated by X-inactivation analysis, identified somatic TET2 mutations. Recurrence testing identified TET2 mutations in 10 out of 182 individuals with X-inactivation skewing. TET2 mutations were specific to individuals with clonal hematopoiesis without hematological malignancies and were associated with alterations in DNA methylation.
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Isolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b), type 2 IFN (IFNg), TNFa, and IL-1, have been well-documented in mouse hematopoietic development.
“The isolated effects of individual inflammatory cytokines, including type 1 interferons (IFNa/b) 1-3 , type 2 IFN (IFNg) 4-6 , TNFa 7,8 , and IL-1 9-11 , have been well-documented in mouse hematopoietic development.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [3]
The paper’s Abstract discusses TET2 mutations in elderly people with clonal hematopoiesis and cites murine findings about Tet2 loss and stem-cell behavior. Searches for inflammatory cytokines, interferons, TNFα, and IL-1 found no passage addressing their isolated effects in mouse hematopoietic development. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThis was the first demonstration that mutation-driven clonal hematopoiesis occurs in healthy persons.
“This was the first demonstration that mutation-driven clonal hematopoiesis occurs in healthy persons 20.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [20]
In 2012, mutations in TET2 were found in approximately 5% of elderly women with non-random X-chromosome inactivation.
“In 2012, mutations in TET2 (a gene coding for an enzyme that oxidizes methylated DNA) were found in ~5% of elderly women with non-random XCI.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [20]
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BackgroundSelf-citationRecent advances in understanding the mechanisms determining longevity
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- Authors
- Busque, L., Patel, J. P., Figueroa, M. E., Vasanthakumar, A., Provost, S., Hamilou, Z., Mollica, L., Li, J., Viale, A., Heguy, A., Hassimi, M., Socci, N., Bhatt, P. K., Gonen, M., Mason, C. E., Melnick, A., Godley, L. A., Brennan, C. W., Abdel-Wahab, O., & Levine, R. L.
- Affiliations
- Hôpital Maisonneuve-Rosemont (CA)
- Memorial Sloan Kettering Cancer Center (US)
- University of Chicago (US)
- Montreal Heart Institute (CA)
- Cornell University (US)
- Corresponding author
- Busque, Lambert
- Levine, Ross L
- ORCID
- Venue
- Nature Genetics
- Published
- 2012-09-23
- Volume
- 44
- Issue
- 11
- Pages
- 1179-1181
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3483435
- OpenAlex
- W1998367819
- Cited by
- 830
- References
- 14
- Citations by year
- 2026: 28 · 2025: 32 · 2024: 52 · 2023: 58 · 2022: 73 · 2021: 69 · 2020: 72 · 2019: 78 · 2018: 75 · 2017: 73 · 2016: 74 · 2015: 68 · 2014: 47 · 2013: 27 · 2012: 4
- FWCI
- 31.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA138234, U54CA143798, R01CA129831)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK092030)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- TET2 mutation, clonal hematopoiesis, somatic mutations, aging, X-inactivation skewing, DNA methylation, myeloid malignancy risk, older women, mutation recurrence
- MeSH terms
- Aging, DNA-Binding Proteins, Female, Hematopoiesis, Humans, Proto-Oncogene Proteins, DNA Methylation, 5-Methylcytosine, Dioxygenases, X Chromosome Inactivation, Exome
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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