{"entity":{"id":"paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","kind":"paper","name":"Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-25","links":[{"label":"Jensen et al., JAMA Oncol 2021: clonal haematopoiesis in DNA repair genes interfering with prostate cancer plasma cell-free DNA testing (69 men, paired whole-blood control)","url":"https://doi.org/10.1001/jamaoncol.2020.5161"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33151258/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["atm","brca","chek2"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","clonal-haematopoiesis"],"terms":["ctdna","cfdna","germline-vs-somatic","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2020.5161","pmid":"33151258","authors":"Jensen K, Konnick EQ, Schweizer MT, et al.","paperType":"observational","findings":["Clonal haematopoiesis variants at 2% or more in plasma from 13 of 69 men, 19%.","Seven men, 10%, had such a variant in a gene used to decide PARP inhibitor candidacy, most often ATM.","Clonal haematopoiesis accounted for almost half of all somatic DNA repair variants detected in plasma.","A paired whole blood control distinguishes them."],"whatItMeans":"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.","caveats":["Sixty-nine men at one academic reference laboratory.","A 2% variant fraction threshold is a choice, and lower-level interference will be commoner still.","It does not quantify how often this has changed treatment in practice."],"changedPractice":true,"participants":69},"route":"/key-papers/paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"chek2","kind":"target","name":"CHEK2","route":"/targets/chek2/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}],"biomarker":[{"id":"ctdna-tumour-fraction","kind":"biomarker","name":"Circulating tumour DNA fraction (and what a negative plasma result means)","route":"/biomarkers/ctdna-tumour-fraction/"},{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}]}}