The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.
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ICR Authors
Authors
De Mattos-Arruda, L
Sammut, S-J
Ross, EM
Bashford-Rogers, R
Greenstein, E
Markus, H
Morganella, S
Teng, Y
Maruvka, Y
Pereira, B
Rueda, OM
Chin, S-F
Contente-Cuomo, T
Mayor, R
Arias, A
Ali, HR
Cope, W
Tiezzi, D
Dariush, A
Dias Amarante, T
Reshef, D
Ciriaco, N
Martinez-Saez, E
Peg, V
Ramon Y Cajal, S
Cortes, J
Vassiliou, G
Getz, G
Nik-Zainal, S
Murtaza, M
Friedman, N
Markowetz, F
Seoane, J
Caldas, C
Sammut, S-J
Ross, EM
Bashford-Rogers, R
Greenstein, E
Markus, H
Morganella, S
Teng, Y
Maruvka, Y
Pereira, B
Rueda, OM
Chin, S-F
Contente-Cuomo, T
Mayor, R
Arias, A
Ali, HR
Cope, W
Tiezzi, D
Dariush, A
Dias Amarante, T
Reshef, D
Ciriaco, N
Martinez-Saez, E
Peg, V
Ramon Y Cajal, S
Cortes, J
Vassiliou, G
Getz, G
Nik-Zainal, S
Murtaza, M
Friedman, N
Markowetz, F
Seoane, J
Caldas, C
Document Type
Journal Article
Date
2019-05-28
Date Accepted
2019-04-22
Abstract
The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.
Citation
Cell reports, 2019, 27 (9), pp. 2690 - 2708.e10
Source Title
Cell reports
Publisher
CELL PRESS
ISSN
2211-1247
eISSN
2211-1247
Collections
Research Team
Cancer Dynamics