Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and impacts clinical outcome
By Catherine C Coombs, A. Zehir, S. Devlin, A. Kishtagari, Aijazuddin Syed, P. Jonsson, D. Hyman, D. Solit, Mark E. Robson, J. Baselga and 5 more. Cell Stem Cell, 2017
725 citations recorded by the source corpus.
Summary Clonal hematopoiesis (CH), as evidenced by recurrent somatic mutations in leukemia-associated genes, commonly occurs among aging human hematopoietic stem cells. We analyzed deep coverage, targeted next-generation sequencing (NGS) data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of CH in patients with non-hematologic malignancies. We identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations (CH-PD). CH was associated with increased age, prior radiation therapy, and tobacco use. PPM1D and TP53 mutations were associated with prior exposure to chemotherapy. CH and CH-PD led to an increased incidence for subsequent hematologic cancers, and CH-PD was associated with shorter patient survival. These data suggest CH occurs in an age-dependent manner and specific perturbations can enhance fitness of clonal hematopoietic stem cells, which can impact outcome through progression to hematologic malignancies and through cell non-autonomous effects on solid tumor biology.
Subfields: Cancer Research, Hematology
View Paper: https://www.semanticscholar.org/paper/0ff84810e58c49c192759488c743c4f3611938cd
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In Cancer Research
Citations in the corpus
- ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. (2022, background): “33,35 Genes mutated in CHIP partially overlap with solid tumour drivers.”
- Cancer therapy shapes the fitness landscape of clonal hematopoiesis (2020, neutral): “Utilizing prospective targeted sequencing data (MSK-IMPACT) from 24,146 cancer patients representing a wide range of primary tumor types (n=56) and ages (Extended Data Table 1), we established a stringent variant calling and filtration workflow to detect CH variants in blood, with a minimum variant…”
- Clonal hematopoiesis in human aging and disease (2019, neutral): “One study of a patient population treated for solid cancers found that CHIP mutations were more prevalent in this group than in populations not selected for cancer (78).”