Dnmt3a Mutations in the Hematopoietic System Promote Colitis-Associated Colon Cancer: A Model of Clonal Hematopoiesis in Solid Tumors

Clonal hematopoiesis (CH) is a condition wherein hematopoietic stem cells (HSCs) acquire mutations, often in presumed leukemia driver genes such as in DNMT3A, leading to clonal dominance and disproportionate contribution to peripheral blood without overt hematologic abnormalities (Jaiswal et al. 2014). In large cohorts of patients with solid tumors including colorectal cancer, presence of CH is associated with inferior overall survival due to progression of primary malignancy (Coombs et al. 2017). While potential involvement of CH in the pathogenesis of solid tumors driven by unrelated genetic alterations has far-reaching translational implications, the mechanistic understanding of this relationship is lacking.