Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing: A Single-Institution Experience.

Abstract

Clonal hematopoiesis (CH) and clonal cytopenia of undetermined significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factors for cardiovascular disease and myeloid malignancy. CH is an incidental finding, and evaluation of the incidence of CH/CCUS-associated mutations in solid tumor next-generation sequencing samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed between February 2022 and April 2023 on next-generation sequencing data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. A total of 2479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS-associated mutations, with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified, and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommendations for these criteria as future guidelines for reporting are described. These variants are incidental findings that require more extensive follow-up or change in therapy management using a single institutional cohort.