The investigators collected 189 plasma samples from 59 patients with metastasized CRPC treated with abiraterone/enzalutamide. In order to stratify plasma DNA samples based on the presence of low (i.e. z-score ≤5; corresponds to \<10% ctDNA) versus high (z-score \>5; corresponds to ≥10% ctDNA) genomic complexity in ctDNA the investigators employed the modified Fast Aneuploidy Screening Test-Sequencing System (mFAST-SeqS), which provides a plasma based marker of aneuploidy (z-score). Altogether 106 plasma samples with a low z-score will be evaluated only with the AVENIO ctDNA Expanded Kit, which is capable of detecting mutations with VAFs as low as 0.1% . From the 83 plasma samples with increased z-score will be sequenced with high coverage (70x) so that both mutations and nucleosome positions can be extracted from the obtained sequences. With the other 32 high z-score samples plasma-Seq will be conducted to establish genome-wide copy number profiles and 31 prostate cancer genes will be enriched to screen for mutations in these genes.
At present, there is no evidence what parameters should be used to decide which treatment options are best for metastatic prostate cancer patients. The suggested innovative technologies, i.e. nucleosome position mapping and gene expression analyses will provide systematic maps of nucleosome positions. The sequencing of plasma samples with 70x will provide in addition a comprehensive view on the mutation spectrum in metastatic prostate cancer. By inclusion of primary tumor analyses, an unprecedented view on prostate cancer genome Evolution will be obtained. Overall, the comprehensive data set (copy number changes, mutations, gene expression) will allow pathway analyses with unprecedented resolution.
