Recurrent Somatic TET2 Mutations in Normal Elderly Individuals With Clonal Hematopoiesis

By Lambert Busque, Jay P. Patel, M. Figueroa, A. Vasanthakumar, Sylvie Provost, Z. Hamilou, L. Mollica, Juan Li, Agnes Viale, Adriana Heguy and 10 more. Nature Genetics, 2012

801 citations recorded by the source corpus.

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.

Subfields: Genetics, Hematology

View Paper: https://www.semanticscholar.org/paper/408ccb94480adbb1ec36b48872f01e19a728df5a

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Citations in the corpus

Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults (2016, positive): “41), from the ﬁltered Mpileup output (described above), with the following parameters: min-coverage 1,000; min-reads2 5; min-var-freq 0.001; strand-ﬁlter 0; and output-vcf 1.”
Clonal hematopoiesis in human aging and disease (2019, positive): “This was the first demonstration that mutation-driven clonal hematopoiesis occurs in healthy persons (21).”
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. (2015, background): “been found in the blood of older individuals, without any evidence of disease (Busque et al., 2012).”
Genomic Classification and Prognosis in Acute Myeloid Leukemia (2016, methodology): “DNMT3A TET2 ASXL1 inv(16) t(15;17) t(8;21) t(11q23;x) inv(3) t(6;9)”
Revisiting the hallmarks of cancer. (2017, positive): “More recently, phenotypically normal cells were shown to carry a high burden of non-silent somatic mutations that are positively selected upon without the formation of cancer [10-12].”
Role of TET enzymes in DNA methylation, development, and cancer (2016, background): “Second, TET2 mutations are frequently observed in aged healthy individuals with clonal hematopoiesis and increase the propensity to develop hematopoieticmalignancies (Busque et al. 2012; Genovese et al. 2014; Jaiswal et al. 2014; Xie et al. 2014).”
Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and impacts clinical outcome (2017, background): “This observation led to the identification of recurrent somatic TET2 mutations in women with NRXI (Busque et al., 1996, 2012), suggesting TET2 mutations promote expansion of clonal populations of hematopoietic stem or progenitor cells, or CH, in the absence of overt hematologic transformation.”
Tet2-mediated Clonal Hematopoiesis Accelerates Heart Failure through a Mechanism Involving the IL-1β/NLRP3 Inflammasome (2018, background): “TET2 gene was the first gene reported to exhibit somatic mutations in blood cells in individuals with clonal hematopoiesis in the absence of hematological malignancies (14).”
Age-related clonal hematopoiesis associated with adverse outcomes. (2014, positive): “Clonal hematopoiesis in the elderly was first demonstrated in studies that showed that approximately 25% of healthy women over the age of 65 years have a skewed pattern of X-chromosome inactivation in peripheral-blood cells,(4,5) which in some cases is associated with mutations in TET2.(6) Large-sca”
Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. (2014, neutral): “Neutrophils (10(9)/L) average (range) 9 (2-36) 6 (3-16) 8 (3-21)”