Franceschini, Gian Marco;
Quaini, Orsetta;
Mizuno, Kei;
Orlando, Francesco;
Ciani, Yari;
Ku, Sheng-Yu;
Sigouros, Michael;
... Beltran, Himisha; + view all
(2024)
Non-invasive detection of neuroendocrine prostate cancer through targeted cell-free DNA methylation.
Cancer Discovery
OF1-OF22.
10.1158/2159-8290.CD-23-0754.
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Abstract
Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. We developed a targeted DNA methylation assay to detect CRPC-NE using plasma cell-free DNA (cfDNA). The assay quantifies tumor content and provides a phenotype evidence score that captures diverse CRPC phenotypes, leveraging regions to inform transcriptional state. We tested the design in independent clinical cohorts (n=222 plasma samples) and qualified it achieving an AUC>0.93 for detecting pathology-confirmed CRPC-NE (n=136). Methylation-defined cfDNA tumor content was associated with clinical outcomes in two prospective phase II clinical trials geared towards aggressive variant CRPC and CRPC-NE. These data support the application of targeted DNA methylation for CRPC-NE detection and patient stratification.
| Type: | Article |
|---|---|
| Title: | Non-invasive detection of neuroendocrine prostate cancer through targeted cell-free DNA methylation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1158/2159-8290.CD-23-0754 |
| Publisher version: | http://dx.doi.org/10.1158/2159-8290.cd-23-0754 |
| Language: | English |
| Additional information: | © 2023 The Authors; Published by the American Association for Cancer Research This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10185949 |
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