Copy number architectures define treatment-mediated selection of lethal prostate cancer clones.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 08 2023
10 08 2023
Historique:
received:
02
06
2022
accepted:
21
07
2023
medline:
14
8
2023
pubmed:
11
8
2023
entrez:
10
8
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 37563129
doi: 10.1038/s41467-023-40315-9
pii: 10.1038/s41467-023-40315-9
pmc: PMC10415299
doi:
Substances chimiques
Receptors, Androgen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4823Subventions
Organisme : Cancer Research UK
ID : CTRNBC-2022/100001
Pays : United Kingdom
Organisme : Arthritis Research UK
ID : CC2041
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29911
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 21999
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 17786
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29569
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 30025
Pays : United Kingdom
Investigateurs
Simone Zaccaria
(S)
Sonya Hessey
(S)
Kai-Keen Shiu
(KK)
John Bridgewater
(J)
Daniel Hochhauser
(D)
Martin Forster
(M)
Siow-Ming Lee
(SM)
Tanya Ahmad
(T)
Dionysis Papadatos-Pastos
(D)
Sam Janes
(S)
Peter Van Loo
(P)
Katey Enfield
(K)
Nicholas McGranahan
(N)
Ariana Huebner
(A)
Sergio Quezada
(S)
Stephan Beck
(S)
Peter Parker
(P)
Tariq Enver
(T)
Robert E Hynds
(RE)
David R Pearce
(DR)
Mary Falzon
(M)
Ian Proctor
(I)
Ron Sinclair
(R)
Chi-Wah Lok
(CW)
Zoe Rhodes
(Z)
David Moore
(D)
Teresa Marafioti
(T)
Miriam Mitchison
(M)
Peter Ellery
(P)
Monica Sivakumar
(M)
Mark Linch
(M)
Sebastian Brandner
(S)
Andrew Rowan
(A)
Crispin Hiley
(C)
Selvaraju Veeriah
(S)
Heather Shaw
(H)
Cristina Naceur-Lombardelli
(C)
Antonia Toncheva
(A)
Paulina Prymas
(P)
Thomas B K Watkins
(TBK)
Chris Bailey
(C)
Carlos Martinez Ruiz
(C)
Kevin Litchfield
(K)
Maise Al-Bakir
(M)
Nnenna Kanu
(N)
Sophia Ward
(S)
Emilia Lim
(E)
James Reading
(J)
Benny Chain
(B)
Tom Watkins
(T)
Melek Akay
(M)
Adrienne Flanagan
(A)
Dhruva Biswas
(D)
Oriol Pich
(O)
Michelle Dietzen
(M)
Clare Puttick
(C)
Emma Colliver
(E)
Alistair Magness
(A)
Mihaela Angelova
(M)
James Black
(J)
Olivia Lucas
(O)
William Hill
(W)
Wing-Kin Liu
(WK)
Alexander Frankell
(A)
Neil Magno
(N)
Foteini Athanasopoulou
(F)
Roberto Salgado
(R)
Claudia Lee
(C)
Kristiana Grigoriadis
(K)
Othman Al-Sawaf
(O)
Takahiro Karasaki
(T)
Abigail Bunkum
(A)
Imran Noorani
(I)
Sarah Benafif
(S)
Vittorio Barbe
(V)
Supreet Kaur Bola
(SK)
Gianmarco Leone
(G)
Constantine Alifrangis
(C)
Ursula McGovern
(U)
Kerstin Thol
(K)
Samuel Gamble
(S)
Seng Kuong Ung
(SK)
Teerapon Sahwangarrom
(T)
Claudia Peinador Marin
(CP)
Sophia Wong
(S)
Piotr Pawlik
(P)
Jie Min Lam
(JM)
Corentin Richard
(C)
Roberto Vendramin
(R)
Krijn Dijkstra
(K)
Jayant Rane
(J)
Jerome Nicod
(J)
Angela Dwornik
(A)
Kerry Bowles
(K)
Rija Zaidi
(R)
Faye Gishen
(F)
Paddy Stone
(P)
Caroline Stirling
(C)
Samra Turajlic
(S)
James Larkin
(J)
Lisa Pickering
(L)
Andrew Furness
(A)
Kate Young
(K)
Will Drake
(W)
Kim Edmonds
(K)
Nikki Hunter
(N)
Mary Mangwende
(M)
Karla Pearce
(K)
Lauren Grostate
(L)
Lewis Au
(L)
Lavinia Spain
(L)
Scott Shepherd
(S)
Haixi Yan
(H)
Benjamin Shum
(B)
Zayd Tippu
(Z)
Brian Hanley
(B)
Charlotte Spencer
(C)
Max Emmerich
(M)
Camille Gerard
(C)
Andreas Michael Schmitt
(AM)
Lyra Del Rosario
(L)
Eleanor Carlyle
(E)
Charlotte Lewis
(C)
Lucy Holt
(L)
Analyn Lucanas
(A)
Molly O'Flaherty
(M)
Steve Hazell
(S)
Hardeep Mudhar
(H)
Christina Messiou
(C)
Arash Latifoltojar
(A)
Annika Fendler
(A)
Fiona Byrne
(F)
Husayn Pallikonda
(H)
Irene Lobon
(I)
Alexander Coulton
(A)
Anne-Laure Cattin
(AL)
Daqi Deng
(D)
Hugang Feng
(H)
Andew Rowan
(A)
Nadia Yousaf
(N)
Sanjay Popat
(S)
Olivia Curtis
(O)
Charlotte Milner-Watts
(C)
Gordon Stamp
(G)
Emma Nye
(E)
Aida Murra
(A)
Justine Korteweg
(J)
Denise Kelly
(D)
Lauren Terry
(L)
Jennifer Biano
(J)
Kema Peat
(K)
Kayleigh Kelly
(K)
Charlotte Grieco
(C)
Mo Linh Le
(ML)
Paolo Davide D'Arienzo
(PD)
Emma Turay
(E)
Peter Hill
(P)
Debra Josephs
(D)
Sheeba Irshad
(S)
James Spicer
(J)
Ula Mahadeva
(U)
Anna Green
(A)
Ruby Stewart
(R)
Natasha Wright
(N)
Georgina Pulman
(G)
Ruxandra Mitu
(R)
Sherene Phillips-Boyd
(S)
Deborah Enting
(D)
Sarah Rudman
(S)
Sharmistha Ghosh
(S)
Eleni Karapanagiotou
(E)
Elias Pintus
(E)
Andrew Tutt
(A)
Sarah Howlett
(S)
James Brenton
(J)
Carlos Caldas
(C)
Rebecca Fitzgerald
(R)
Merche Jimenez-Linan
(M)
Elena Provenzano
(E)
Alison Cluroe
(A)
Anna Paterson
(A)
Sarah Aitken
(S)
Kieren Allinson
(K)
Grant Stewart
(G)
Ultan McDermott
(U)
Emma Beddowes
(E)
Tim Maughan
(T)
Olaf Ansorge
(O)
Peter Campbell
(P)
Patricia Roxburgh
(P)
Sioban Fraser
(S)
Kevin Blyth
(K)
John Le Quesne
(J)
Matthew Krebs
(M)
Fiona Blackhall
(F)
Yvonne Summers
(Y)
Pedro Oliveira
(P)
Ana Ortega-Franco
(A)
Caroline Dive
(C)
Fabio Gomes
(F)
Mat Carter
(M)
Jo Dransfield
(J)
Anne Thomas
(A)
Dean Fennell
(D)
Jacqui Shaw
(J)
Claire Wilson
(C)
Domenic Marrone
(D)
Babu Naidu
(B)
Shobhit Baijal
(S)
Bruce Tanchel
(B)
Gerald Langman
(G)
Andrew Robinson
(A)
Martin Collard
(M)
Peter Cockcroft
(P)
Charlotte Ferris
(C)
Hollie Bancroft
(H)
Amy Kerr
(A)
Gary Middleton
(G)
Joanne Webb
(J)
Salma Kadiri
(S)
Peter Colloby
(P)
Bernard Olisemeke
(B)
Rodelaine Wilson
(R)
Helen Shackleford
(H)
Aya Osman
(A)
Ian Tomlinson
(I)
Sanjay Jogai
(S)
Samantha Holden
(S)
Tania Fernandes
(T)
Iain McNeish
(I)
Blanche Hampton
(B)
Mairead McKenzie
(M)
Allan Hackshaw
(A)
Abby Sharp
(A)
Kitty Chan
(K)
Laura Farrelly
(L)
Hayley Bridger
(H)
Rachel Leslie
(R)
Adrian Tookman
(A)
Informations de copyright
© 2023. Springer Nature Limited.
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