Profiling clonal hematopoiesis in cancer survivors with single-cell DNA sequencing

Cure rates for children with cancer have increased dramatically over the past 40 years with the advent of modern treatment strategies, but most patients have serious life-long medical conditions as a result of the toxicity of their treatments. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described entity that has been associated with chronic diseases, most notably coronary artery disease. To determine if the presence and features of CHIP are different in childhood cancer survivors compared to age and sex-matched controls, we performed targeted single-cell DNA sequencing of thousands of mature and progenitor hematopoietic cells from a cohort of patients that are greater than 50 years of age and received greater than 25g/m2 of highly mutagenic alkylating chemotherapy as a child.