{"entity":{"id":"paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022","kind":"paper","name":"Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis","aka":[],"tldr":"A blood test that reads chemical marks on DNA rather than its letters separated the aggressive neuroendocrine form of prostate cancer from the ordinary form almost perfectly.","summary":"Neuroendocrine prostate cancer is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma and is difficult to detect in practice. Methylated DNA immunoprecipitation and high-throughput sequencing was performed on a training set of tumours, differentially methylated regions between neuroendocrine prostate cancer and castration-resistant adenocarcinoma were identified, and a model was built to predict the presence of neuroendocrine disease, termed a risk score. The same assay was then applied to cell-free DNA from two independent cohorts. The test cohort comprised 48 men, 9 with neuroendocrine disease and 39 with castration-resistant adenocarcinoma; risk scores were significantly higher in the neuroendocrine group and discriminated with an area under the receiver operating curve of 0.96, with the optimal cut-off giving 100% sensitivity and 90% specificity. The validation cohort included 53 men, 12 with neuroendocrine disease and 41 with adenocarcinoma; discrimination was perfect, area under the curve 1.0, and the predefined cut-off gave 100% sensitivity and 95% specificity.","asOf":"2026-09-25","links":[{"label":"Berchuck et al., Clin Cancer Res 2022: tissue-informed cell-free DNA methylation to detect neuroendocrine prostate cancer (101 plasma samples in two cohorts)","url":"https://doi.org/10.1158/1078-0432.CCR-21-3762"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34907080/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":["liquid-biopsy","methylation-profiling"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","epigenetic-reprogramming"],"terms":["ctdna","cfdna","histologic-transformation","liquid-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-3762","pmid":"34907080","authors":"Berchuck JE, Baca SC, McClure HM, et al.","paperType":"translational","findings":["Risk score from cell-free DNA methylation discriminated neuroendocrine from castration-resistant adenocarcinoma with an area under the curve of 0.96 in the test cohort.","One hundred per cent sensitivity and 90% specificity at the optimal cut-off.","Perfect discrimination in an independent 53-man validation cohort, with 100% sensitivity and 95% specificity at the predefined cut-off."],"whatItMeans":"It is the right shape of answer for a transition that is epigenetic rather than genetic, and it could in principle spare the biopsy that is currently the only way to make this diagnosis.","caveats":["Twenty-one men with neuroendocrine disease in total across both cohorts, so a perfect area under the curve should be read as promising rather than settled.","Methylated DNA immunoprecipitation sequencing is a research assay, not one that can be ordered.","The comparison is against a histological reference standard that is itself imperfect."],"changedPractice":false,"participants":101},"route":"/key-papers/paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-nepc","kind":"cancer","name":"Neuroendocrine and small-cell prostate cancer","route":"/cancers/prostate-nepc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"}],"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":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}],"biomarker":[{"id":"nepc-transformation","kind":"biomarker","name":"Treatment-emergent neuroendocrine transformation (recognising it)","route":"/biomarkers/nepc-transformation/"}]}}