Cited by 830Acute Myeloid Leukemia ResearchCancer Genomics and DiagnosticsEpigenetics and DNA Methylation

Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis

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Busque, Lambert, Patel, Jay P, Figueroa, Maria E, Vasanthakumar, Aparna, Provost, Sylvie, Hamilou, Zineb, Mollica, Luigina, Li, Juan +12 more·2012·Nature Genetics

Abstract

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)

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  • This 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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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
Venue
Nature Genetics
Published
2012-09-23
Volume
44
Issue
11
Pages
1179-1181
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
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
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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