Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
30
11
2019
accepted:
18
11
2020
entrez:
8
1
2021
pubmed:
9
1
2021
medline:
11
2
2021
Statut:
ppublish
Résumé
Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.
Identifiants
pubmed: 33414553
doi: 10.1038/s41588-020-00750-6
pii: 10.1038/s41588-020-00750-6
pmc: PMC7808565
mid: NIHMS1648210
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
86-99Subventions
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/T001267/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA224065
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA114046
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224083
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211199
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA224067
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224070
Pays : United States
Investigateurs
Matthew H Bailey
(MH)
Vito W Rebecca
(VW)
Michael A Davies
(MA)
Peter N Robinson
(PN)
Brian J Sanderson
(BJ)
Steven B Neuhauser
(SB)
Lacey E Dobrolecki
(LE)
Xiaofeng Zheng
(X)
Mourad Majidi
(M)
Ran Zhang
(R)
Xiaoshan Zhang
(X)
Argun Akcakanat
(A)
Kurt W Evans
(KW)
Timothy A Yap
(TA)
Dali Li
(D)
Erkan Yucan
(E)
Christopher D Lanier
(CD)
Turcin Saridogan
(T)
Bryce P Kirby
(BP)
Min Jin Ha
(MJ)
Huiqin Chen
(H)
Scott Kopetz
(S)
David G Menter
(DG)
Jianhua Zhang
(J)
Shannon N Westin
(SN)
Michael P Kim
(MP)
Bingbing Dai
(B)
Don L Gibbons
(DL)
Coya Tapia
(C)
Vanessa B Jensen
(VB)
Gao Boning
(G)
John D Minna
(JD)
Hyunsil Park
(H)
Brenda C Timmons
(BC)
Luc Girard
(L)
Dylan Fingerman
(D)
Qin Liu
(Q)
Rajasekharan Somasundaram
(R)
Min Xiao
(M)
Vashisht G Yennu-Nanda
(VG)
Michael T Tetzlaff
(MT)
Xiaowei Xu
(X)
Katherine L Nathanson
(KL)
Song Cao
(S)
Feng Chen
(F)
John F DiPersio
(JF)
Kian H Lim
(KH)
Cynthia X Ma
(CX)
Fernanda M Rodriguez
(FM)
Brian A Van Tine
(BA)
Andrea Wang-Gillam
(A)
Michael C Wendl
(MC)
Yige Wu
(Y)
Matthew A Wyczalkowski
(MA)
Lijun Yao
(L)
Reyka Jayasinghe
(R)
Rebecca L Aft
(RL)
Ryan C Fields
(RC)
Jingqin Luo
(J)
Katherine C Fuh
(KC)
Vicki Chin
(V)
John DiGiovanna
(J)
Jeffrey Grover
(J)
Soner Koc
(S)
Sara Seepo
(S)
Tiffany Wallace
(T)
Chong-Xian Pan
(CX)
Moon S Chen
(MS)
Luis G Carvajal-Carmona
(LG)
Amanda R Kirane
(AR)
May Cho
(M)
David R Gandara
(DR)
Jonathan W Riess
(JW)
Tiffany Le
(T)
Ralph W deVere White
(RW)
Clifford G Tepper
(CG)
Hongyong Zhang
(H)
Nicole B Coggins
(NB)
Paul Lott
(P)
Ana Estrada
(A)
Ted Toal
(T)
Alexa Morales Arana
(AM)
Guadalupe Polanco-Echeverry
(G)
Sienna Rocha
(S)
Ai-Hong Ma
(AH)
Nicholas Mitsiades
(N)
Salma Kaochar
(S)
Bert W O'Malley
(BW)
Matthew J Ellis
(MJ)
Susan G Hilsenbeck
(SG)
Michael Ittmann
(M)
Roebi de Bruijn
(R)
Petra Ter Brugge
(P)
Simona Corso
(S)
Alessandro Fiori
(A)
Silvia Giordano
(S)
Marieke van de Ven
(M)
Daniel S Peeper
(DS)
Ian Miller
(I)
Cristina Bernadó
(C)
Beatriz Morancho
(B)
Lorena Ramírez
(L)
Joaquín Arribas
(J)
Héctor G Palmer
(HG)
Alejandro Piris-Gimenez
(A)
Laura Soucek
(L)
Ahmed Dahmani
(A)
Elodie Montaudon
(E)
Fariba Nemati
(F)
Virginie Dangles-Marie
(V)
Didier Decaudin
(D)
Sergio Roman-Roman
(S)
Denis G Alférez
(DG)
Katherine Spence
(K)
Robert B Clarke
(RB)
Mohamed Bentires-Alj
(M)
David K Chang
(DK)
Andrew V Biankin
(AV)
Alejandra Bruna
(A)
Martin O'Reilly
(M)
Carlos Caldas
(C)
Oriol Casanovas
(O)
Eva Gonzalez-Suarez
(E)
Purificacíon Muñoz
(P)
Alberto Villanueva
(A)
Nathalie Conte
(N)
Jeremy Mason
(J)
Ross Thorne
(R)
Terrence F Meehan
(TF)
Helen Parkinson
(H)
Zdenka Dudova
(Z)
Ales Křenek
(A)
Dalibor Stuchlík
(D)
Olivier Elemento
(O)
Giorgio Inghirami
(G)
Anna Golebiewska
(A)
Simone P Niclou
(SP)
G Bea A Wisman
(GBA)
Steven de Jong
(S)
Petra Kralova
(P)
Radislav Sedlacek
(R)
Elisa Claeys
(E)
Eleonora Leucci
(E)
Massimiliano Borsani
(M)
Luisa Lanfrancone
(L)
Pier Giuseppe Pelicci
(PG)
Gunhild Mari Mælandsmo
(GM)
Jens Henrik Norum
(JH)
Emilie Vinolo
(E)
Commentaires et corrections
Type : ErratumIn
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