A new large-scale study recently published in Nature Genetics highlights a paradigm shift in hereditary hematologic diagnostics, where germline genetics is becoming a key determinant in the diagnosis of clonal evolution and cancer progression.
Analyzing more than 730,000 individuals, the authors show that inherited variants in certain genes (such as CHEK2, ATM, RUNX1, TP53, ETV6 and DDX41) shape:
• the emergence of clonal hematopoiesis
• the selection of specific somatic mutations
• the probability of progression to hematologic malignancies
Most importantly, the same somatic clone carries dramatically different cancer risks depending on the germline background.
This work strongly supports the integration of germline multigene testing into the diagnostic and risk-stratification pathway of inherited hematologic disorders, opening new perspectives for the early identification of high-risk individuals, for personalized surveillance strategies and for the accurate interception of myeloid and lymphoid neoplasms.
At 4bases, we focus on making available gene panels that can support a variety of genetic profile questions; this is the case with HEMATO pro, a CE-IVD kit designed for the analysis of complex genomic variants associated with Lymphoid and Myeloid Diseases.
With the analysis of 146 relevant genes frequently mutated in hematologic malignancies, the kit is validated for both germline and somatic analysis (SNVs, indels, CNVs and ITD) of DNA extracted from blood samples.
Eager to learn more details? Read the full study!
Germline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy
Nat Genet. 2025 Jul 15;57(8):1872–1880. doi: 10.1038/s41588-025-02250-x
