Interpreting BRCA1/2 Clonal Hematopoiesis in the ASCO Circulating Tumor DNA Testing Guideline

The ASCO Guideline by Lockwood et al 1 on circulating tumor DNA (ctDNA) testing in solid tumors and lymphoma appropriately identifies clonal hematopoiesis (CH) as an important potential source of non-tumor-derived variants in plasma that can generate false-positive, therapyindicating findings, a concern also raised in the ESMO recommendations on ctDNA assays 2 and in clinical laboratory practice.3 In discussing false-positive results relevant to treatment selection, Lockwood et al 1 state (page 1483) that …"mutations in PIK3CA are nearly always of tumor origin, whereas somatic variants in BRCA1/BRCA2 may originate from clonal hematopoiesis."citing Magee et al 4 as supporting evidence.Subsequent published correspondence concerning the BRCA1/ BRCA2 findings of Magee et al, 4 however, provides an important qualification to this statement.