{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001006598"],"host":["EGA"],"description":["EGA study EGAS00001006598"],"dataset_title":["CASCADE low-pass whole genome sequencing data","CASCADE tumour transcriptome data","CASCADE germline whole genome sequencing data","CASCADE tumour high-coverage whole genome sequencing data"],"category":["restricted"],"repository":["EGA"],"name_synonyms":["treatment, Therapy, hereditary prostate cancer, cancer of the prostate, Prostate Neoplasms, selection process, Neoplasms, familial, number, Cancers, cancer of prostate, Treatments, presence, cardinality., Prostate Neoplasm, Prostatic Neoplasm, count in organism, Cancer of the Prostate, Therapeutic, Prostatic Cancer, disease management, Therapies, Neoplasm, Prostatic Cancers, Prostatic, prostate cancer, Treatment, PC, NOS, Cancer of Prostate, Prostate Cancer, Prostate, Cancer, Prostate Cancers"],"description_synonyms":["CG34403, deceased, l(4)13, Materials, Polyarteritis Nodosa, Prostate Neoplasms, multiple endocrine neoplasia syndrome, Neoplasms, Periarteritis Nodosa, LEF/TCF-1, number, Receptors, men syndromes, Gene, Multiple endocrine neoplasia, DmelCG34403, broad, Cardiac Death, Androgens Receptors, presence, IA5, LEF-1, metastatic prostate cancer, Hormone, DHTR, 5 alpha Dihydrotestosterone Receptor, Dmel_CG32005, anatomical site, LEF1/TCF, Prostatic Cancers, Classic Polyarteritis Nodosa, 5, Agonists, Cancer of Prostate, organism subdivision, Testosterone Receptor, Prostate Cancers, treatment, TCF/LEF, hormones, metastatic prostate carcinoma, Genetic, Biopsies, Genomes, Hormone Receptor, multiple endocrine neoplasia, Tcf-1, Hormone Receptor Agonists, Boys, d-TCF, cTCF, Stanolone Receptors, endocrine, men syndrome, Prostatic Neoplasm, Cancer of the Prostate, Dihydrotestosterone Receptors, Clients, ELL1, Ell1, TCF/LEF1, disease management, Therapies, Testosterone, Prostatic, chimpanzees, polyarteritis, Pan, PAN, prostate carcinoma metastatic, Principal body part subdivision, Cancer, Therapy, close to, hereditary prostate cancer, cancer of the prostate, body part, Multiple endocrine neoplasms, wide/broad, DmelCG10120, Multiple Endocrine Neoplasia, MDH, Dmel_CG17964, familial, Receptor Agonists, prostate cancer metastatic, Subdivision of cardinal body part, ME, Cistrons, Client, LEF/TCF, familial endocrine, Stanolone Receptor, Dm Pan, near to, count in organism, Androgen, pan.dTCF, PERIANTHIA, Prostatic Cancer, post-mortem, Familial endocrine adenomatosis, Neoplasm, Androgens, Genetic Materials, NOS, Tcf, TCF, MEN, Men, Me, multiple endocrine adenomatosis, Death, Tcf/LEF, Androgen Receptors, Genetic Material, 5 alpha-Dihydrotestosterone Receptor, Lef1, periarteritis, distinct., Stanolone, alpha-Dihydrotestosterone Receptor, 5 alpha-Dihydrotestosterone, LEF1, F24J5.12, Classical Polyarteritis Nodosa, Panarteritis Nodosa, Dihydrotestosterone, Adenomatosis, DTCF, DTcf, mem, common, patient, tcf, INSDC_feature:gene, whole genome, men, Cancers, CG17964, cancer of prostate, Treatments, l(4)102ABb, CG32005, Prostate Neoplasm, F24J5_12, wide, metastatic, Endocrine neoplasia, PPP1R68, multiple, Therapeutic, Patient, Material, approaches, C19orf17, Lef, Indexes, cardinality, vicinity of, NR3C4, Androgen Receptor, anon-WO0118547.278, prostate cancer, Treatment, Multiple endocrine adenomatosis, PC, Cistron, Receptor, lef1, multiple endocrine neoplasia syndrome(s), Prostate Cancer, Mdh-NADP, Prostate, dTCF, dTcf, CG10120"],"additional_accession":[]},"is_claimable":false,"name":"Treatment-mediated selection of lethal prostate cancer clones defined by copy number architectures","description":"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.","dates":{"updated":"2022-12-13 11:52:18"},"accession":"EGAS00001006598","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001009492","EGAD00001009491","EGAD00001009493","EGAD00001009494","EGAC00001002865"]}}