Copy number architectures define treatment-mediated selection of lethal prostate cancer clones
| Title: | Copy number architectures define treatment-mediated selection of lethal prostate cancer clones |
|---|---|
| Authors: | Hasan A. M. M.; Cremaschi P.; Wetterskog D.; Jayaram A.; Wong S. Q.; Williams S.; Pasam A.; Trigos A.; Trujillo B.; Grist E.; Friedrich S.; Vainauskas O.; Parry M.; Ismail M.; Devlies W.; Wingate A.; Linch M.; Naceur-Lombardelli C.; Zaccaria S.; Hessey S.; Shiu K. -K.; Bridgewater J.; Hochhauser D.; Forster M.; Lee S. -M.; Ahmad T.; Papadatos-Pastos D.; Janes S.; Van Loo P.; Enfield K.; McGranahan N.; Huebner A.; Quezada S.; Beck S.; Parker P.; Enver T.; Hynds R. E.; Pearce D. R.; Falzon M.; Proctor I.; Sinclair R.; Lok C. -W.; Rhodes Z.; Moore D.; Marafioti T.; Mitchison M.; Ellery P.; Sivakumar M.; Brandner S.; Rowan A.; Hiley C.; Veeriah S.; Shaw H.; Toncheva A.; Prymas P.; Watkins T. B. K.; Bailey C.; Martinez Ruiz C.; Litchfield K.; Al-Bakir M.; Kanu N.; Ward S.; Lim E.; Reading J.; Chain B.; Watkins T.; Akay M.; Flanagan A.; Biswas D.; Pich O.; Dietzen M.; Puttick C.; Colliver E.; Magness A.; Angelova M.; Black J.; Lucas O.; Hill W.; Liu W. -K.; Frankell A.; Magno N.; Athanasopoulou F.; Salgado R.; Lee C.; Grigoriadis K.; Al-Sawaf O.; Karasaki T.; Bunkum A.; Noorani I.; Benafif S.; Barbe V.; Bola S. K.; Leone G.; Alifrangis C.; McGovern U.; Thol K.; Gamble S.; Ung S. K.; Sahwangarrom T.; Marin C. P.; Wong S.; Pawlik P.; Lam J. M.; Richard C.; Vendramin R.; Dijkstra K.; Rane J.; Nicod J.; Dwornik A.; Bowles K.; Zaidi R.; Gishen F.; Stone P.; Stirling C.; Turajlic S.; Larkin J.; Pickering L.; Furness A.; Young K.; Drake W.; Edmonds K.; Hunter N.; Mangwende M.; Pearce K.; Grostate L.; Au L.; Spain L.; Shepherd S.; Yan H.; Shum B.; Tippu Z.; Hanley B.; Spencer C.; Emmerich M.; Gerard C.; Schmitt A. M.; Del Rosario L.; Carlyle E.; Lewis C.; Holt L.; Lucanas A.; O'Flaherty M.; Hazell S.; Mudhar H.; Messiou C.; Latifoltojar A.; Fendler A.; Byrne F.; Pallikonda H.; Lobon I.; Coulton A.; Cattin A. -L.; Deng D.; Feng H.; Yousaf N.; Popat S.; Curtis O.; Milner-Watts C.; Stamp G.; Nye E.; Murra A.; Korteweg J.; Kelly D.; Terry L.; Biano J.; Peat K.; Kelly K.; Grieco C.; Le M. L.; D'Arienzo P. D.; Turay E.; Hill P.; Josephs D.; Irshad S.; Spicer J.; Mahadeva U.; Green A.; Stewart R.; Wright N.; Pulman G.; Mitu R.; Phillips-Boyd S.; Enting D.; Rudman S.; Ghosh S.; Karapanagiotou E.; Pintus E.; Tutt A.; Howlett S.; Brenton J.; Caldas C.; Fitzgerald R.; Jimenez-Linan M.; Provenzano E.; Cluroe A.; Paterson A.; Aitken S.; Allinson K.; Stewart G.; McDermott U.; Beddowes E.; Maughan T.; Ansorge O.; Campbell P.; Roxburgh P.; Fraser S.; Blyth K.; Le Quesne J.; Krebs M.; Blackhall F.; Summers Y.; Oliveira P.; Ortega-Franco A.; Dive C.; Gomes F.; Carter M.; Dransfield J.; Thomas A.; Fennell D.; Shaw J.; Wilson C.; Marrone D.; Naidu B.; Baijal S.; Tanchel B.; Langman G.; Robinson A.; Collard M.; Cockcroft P.; Ferris C.; Bancroft H.; Kerr A.; Middleton G.; Webb J.; Kadiri S.; Colloby P.; Olisemeke B.; Wilson R.; Shackleford H.; Osman A.; Tomlinson I.; Jogai S.; Holden S.; Fernandes T.; McNeish I.; Hampton B.; McKenzie M.; Hackshaw A.; Sharp A.; Chan K.; Farrelly L.; Bridger H.; Leslie R.; Tookman A.; Swanton C.; Jamal-Hanjani M.; Lise S.; Sandhu S.; Attard G. |
| Contributors: | Hasan, A; Cremaschi, P; Wetterskog, D; Jayaram, A; Wong, S; Williams, S; Pasam, A; Trigos, A; Trujillo, B; Grist, E; Friedrich, S; Vainauskas, O; Parry, M; Ismail, M; Devlies, W; Wingate, A; Linch, M; Naceur-Lombardelli, C; Zaccaria, S; Hessey, S; Shiu, K; Bridgewater, J; Hochhauser, D; Forster, M; Lee, S; Ahmad, T; Papadatos-Pastos, D; Janes, S; Van Loo, P; Enfield, K; Mcgranahan, N; Huebner, A; Quezada, S; Beck, S; Parker, P; Enver, T; Hynds, R; Pearce, D; Falzon, M; Proctor, I; Sinclair, R; Lok, C; Rhodes, Z; Moore, D; Marafioti, T; Mitchison, M; Ellery, P; Sivakumar, M; Brandner, S; Rowan, A; Hiley, C; Veeriah, S; Shaw, H; Toncheva, A; Prymas, P; Watkins, T; Bailey, C; Martinez Ruiz, C; Litchfield, K; Al-Bakir, M; Kanu, N; Ward, S; Lim, E; Reading, J; Chain, B; Akay, M; Flanagan, A; Biswas, D; Pich, O; Dietzen, M; Puttick, C; Colliver, E; Magness, A; Angelova, M; Black, J; Lucas, O; Hill, W; Liu, W; Frankell, A; Magno, N; Athanasopoulou, F; Salgado, R; Lee, C; Grigoriadis, K; Al-Sawaf, O; Karasaki, T; Bunkum, A; Noorani, I; Benafif, S; Barbe, V; Bola, S; Leone, G; Alifrangis, C; Mcgovern, U; Thol, K; Gamble, S; Ung, S |
| Publisher Information: | Nature Research; GB |
| Publication Year: | 2023 |
| Collection: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| Subject Terms: | Clone Cell; DNA Copy Number Variation; Genome; Genomic; Human; Male; Prostatic Neoplasm; Receptors; Androgen |
| Description: | Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify 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 changes, we confirm 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. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10−8and 6.4 × 10−4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories. |
| Document Type: | article in journal/newspaper |
| File Description: | ELETTRONICO |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37563129; info:eu-repo/semantics/altIdentifier/wos/WOS:001050351300024; volume:14; issue:1; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/10281/508439 |
| DOI: | 10.1038/s41467-023-40315-9 |
| Availability: | https://hdl.handle.net/10281/508439; https://doi.org/10.1038/s41467-023-40315-9 |
| Rights: | info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.885B6818 |
| Database: | BASE |