Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
06
11
2019
accepted:
14
01
2020
entrez:
5
2
2022
pubmed:
1
2
2020
medline:
1
2
2020
Statut:
ppublish
Résumé
Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell-cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations.
Identifiants
pubmed: 35122013
doi: 10.1038/s43018-020-0026-6
pii: 10.1038/s43018-020-0026-6
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
163-175Subventions
Organisme : NIDDK NIH HHS
ID : UC4 DK108132
Pays : United States
Organisme : Cancer Research UK
Pays : United Kingdom
Investigateurs
H Raza Ali
(HR)
M Al Sa'd
(M)
S Alon
(S)
Samuel Aparicio
(S)
G Battistoni
(G)
S Balasubramanian
(S)
R Becker
(R)
Bernd Bodenmiller
(B)
E S Boyden
(ES)
D Bressan
(D)
A Bruna
(A)
B Marcel
(B)
Carlos Caldas
(C)
M Callari
(M)
I G Cannell
(IG)
H Casbolt
(H)
N Chornay
(N)
Y Cui
(Y)
A Dariush
(A)
K Dinh
(K)
A Emenari
(A)
Y Eyal-Lubling
(Y)
J Fan
(J)
E Fisher
(E)
E A González-Solares
(EA)
C González-Fernández
(C)
D Goodwin
(D)
W Greenwood
(W)
F Grimaldi
(F)
G J Hannon
(GJ)
O Harris
(O)
S Harris
(S)
C Jauset
(C)
J A Joyce
(JA)
E D Karagiannis
(ED)
T Kovačević
(T)
L Kuett
(L)
R Kunes
(R)
A Küpcü Yoldaş
(A)
D Lai
(D)
E Laks
(E)
H Lee
(H)
M Lee
(M)
G Lerda
(G)
Y Li
(Y)
A McPherson
(A)
N Millar
(N)
C M Mulvey
(CM)
F Nugent
(F)
C H O'Flanagan
(CH)
M Paez-Ribes
(M)
I Pearsall
(I)
F Qosaj
(F)
A J Roth
(AJ)
Oscar M Rueda
(OM)
T Ruiz
(T)
K Sawicka
(K)
L A Sepúlveda
(LA)
S P Shah
(SP)
A Shea
(A)
A Sinha
(A)
A Smith
(A)
S Tavaré
(S)
S Tietscher
(S)
I Vázquez-García
(I)
S L Vogl
(SL)
N A Walton
(NA)
A T Wassie
(AT)
S S Watson
(SS)
S A Wild
(SA)
E Williams
(E)
J Windhager
(J)
C Xia
(C)
P Zheng
(P)
X Zhuang
(X)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.
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