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In one man in ten with advanced prostate cancer, a DNA repair fault found in a blood test came from his bone marrow rather than from his cancer, which could send him to the wrong drug.
A case series of 69 men with advanced prostate cancer, metastatic or with rising PSA after localised therapy, who had cell-free DNA variant testing with a large next-generation sequencing panel. To determine the source of variants in plasma, paired cell-free DNA and whole blood control samples were tested. Clonal haematopoiesis variants at 2% or more variant fraction were detected in cell-free DNA from 13 of the 69 men, 19%. Seven men, 10%, had clonal haematopoiesis variants in DNA repair genes used to determine PARP inhibitor candidacy, including ATM in 5, BRCA2 in 1 and CHEK2 in 1. Overall, clonal haematopoiesis variants accounted for almost half of the somatic DNA repair gene variants detected. Variants correlated exponentially with older age, and could be distinguished from prostate cancer variants using a paired whole blood control.
It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.
Shares CHEK2, Circulating tumour DNA fraction (and what a negative plasma result means), Clonal haematopoiesis (CHIP), ATM.
Shares Circulating tumour DNA fraction (and what a negative plasma result means), ATM, Cell-free DNA (cfDNA), Double-strand break repair: HR versus end joining.
Shares CHEK2, ATM, JAMA Oncology, Double-strand break repair: HR versus end joining.
Shares CHEK2, ATM, Double-strand break repair: HR versus end joining, Germline vs somatic mutations.
Shares Homologous recombination repair gene mutation in prostate cancer, Cell-free DNA (cfDNA), Double-strand break repair: HR versus end joining, BRCA1 / BRCA2 (HRD).
Shares Circulating tumour DNA fraction (and what a negative plasma result means), Cell-free DNA (cfDNA), BRCA1 / BRCA2 (HRD), Circulating tumour DNA (ctDNA).
Shares CHEK2, Homologous recombination repair gene mutation in prostate cancer, ATM, Double-strand break repair: HR versus end joining.
Shares Cell-free DNA (cfDNA), JAMA Oncology, Circulating tumour DNA (ctDNA), Comprehensive genomic profiling.