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Treatment-mediated selection of lethal prostate cancer clones defined by copy number architectures

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient relationships of metastases that evade treatment, we performed genome- wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 142 metastatic regions from 10 organs harvested post-mortem from nine men who died from prostate cancer. We identified diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number change, we confirmed a common clone of origin across metastases and diagnostic biopsies; and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. Autosome-defined clusters were characterized by cluster-specific AR gene architectures that in two index cases were topologically more congruent than by chance (p-values 0.03, 3.07x10-8). Integration with anatomical site suggested patterns of spread and points of genomic divergence. Copy number boundaries identified treatment-selected clones with putatively distinct lethal trajectories.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001009491 Illumina NovaSeq 6000 28
EGAD00001009492 Illumina NovaSeq 6000 20
EGAD00001009493 Illumina NovaSeq 6000 14
EGAD00001009494 Illumina NovaSeq 6000 152
Publications Citations
Copy number architectures define treatment-mediated selection of lethal prostate cancer clones.
Nat Commun 14: 2023 4823