Inferred clonal hematopoiesis from tumor DNA sequencing among men with prostate cancer: correlation with somatic tumor alterations and outcomes

Abstract

Background: Clonal hematopoiesis (CH) may be inferred from clinical next-generation sequencing (NGS) of tumor tissue. The clinical significance of inferred CH when detected as part of routine tumor sequencing is not well established and it is unknown whether or not CH is associated with other somatic mutations in tumors of men with prostate cancer. Methods: We performed a retrospective review of clinical-grade NGS results from primary prostate tissue at a single institution. NGS reports were reviewed for the presence of pathogenic mutations in a panel of 27 genes commonly known to be mutated in CH. Overall survival from time of diagnosis and association with somatic alterations were interrogated. Results: A total of 396 patients were included, with a median follow-up of 7.8 years (range 0.2-21.4 years). Approximately 12% of patients had inferred CH detected (n = 46) with ASXL1, TET2, and DNMT3A being the most commonly affected genes. In univariate analysis, those with inferred CH had an 81% increased risk of death compared to those without inferred CH (hazard ratio 1.8, 95% CI 1.1, 3.1, P = .03). This was attenuated after controlling for age at diagnosis and race (HR 1.1, 95% CI 0.6, 2.0, P = .77). Those with inferred CH were more likely to have pathogenic somatic mutations in PIK3CA (15% vs 4%), CTNNB1 (13% vs 2%) and BRCA1 (4% vs 0.3%). Conclusion: Inferred CH is commonly detected on tumor-tissue NGS testing but does not clearly have a negative prognostic impact after adjusting for age. It may also be associated with the identification of other somatic driver mutations.