Researchers performed genome-wide copy number profiling of the androgen receptor (AR) on metastases from deceased prostate cancer patients.
By Tarun Sai LomteAug 16 2023Reviewed by Sophia Coveney In a recent study published in Nature Communications, researchers performed genome-wide copy number profiling of the androgen receptor on metastases from deceased prostate cancer patients.
The study and findings In the present study, researchers characterized the genomic complexity of AR across lethal metastases. They performed autopsies on 10 patients who developed treatment resistance and died from metastatic castration-resistant prostate cancer . Seventy-four samples had AR gain, including one metastasis from eight subjects. Further, distinct metastasis groups with overlapping patterns of chromosome X copy number were observed, with inter- and intra-patient diversity. Next, up to six metastases from each patient were selected for re-sequencing at higher coverage depth, leading to the identification of unique breakpoints with high density in a large region around AR.
They observed alleles with D891N or T878A, or both in one of the liver metastases. Additional analyses suggested that p.T878A occurred after metastatic seeding and emerged independently in a lineage with p.D891N. They observed that transition points in samples from one patient were shared with all metastases from post-mortem samples from that individual, reaffirming a common clone of origin in lethal metastases.
The authors tested whether a cluster derived from autosomal transition points was more likely to have the same AR alterations. They observed that clusters defined by their autosome were associated with metastases in the same cluster defined by copy number profile.
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