EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100134512EGA dataset EGAD00001001345EGATumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer.Hong Matthew K H MK, Macintyre Geoff G, Wedge David C DC, Van Loo Peter P, Patel Keval K, Lunke Sebastian S, Alexandrov Ludmil B LB, Sloggett Clare C, Cmero Marek M, Marass Francesco F, Tsui Dana D, Mangiola Stefano S, Lonie Andrew A, Naeem Haroon H, Sapre Nikhil N, Phal Pramit M PM, Kurganovs Natalie N, Chin Xiaowen X, Kerger Michael M, Warren Anne Y AY, Neal David D, Gnanapragasam Vincent V, Rosenfeld Nitzan N, Pedersen John S JS, Ryan Andrew A, Haviv Izhak I, Costello Anthony J AJ, Corcoran Niall M NM, Hovens Christopher M CMfalseena-DATASET-UOM-CAP-21-04-2015-13:06:47:615-508 - samplesData from the study of subclonal metastatic expansion in prostate cancer. RNA-seq of twelve samples, tumour and benign tissue, from the four initial patients.2017-07-26 15:39:26EGAD00001001345960625827447EGAC00001000230EGAS00001000942