The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Leticia De Mattos-Arruda; Stephen John Sammut; Edith M. Ross; Rachael Bashford-Rogers; Erez Greenstein; Havell Markus; Sandro Morganella; Yvonne Teng; Yosef Maruvka; Bernard Pereira; Oscar M. Rueda; Suet Feung Chin; Tania Contente-Cuomo; Regina Mayor; Alexandra Arias; H. Raza Ali; Wei Cope; Daniel Tiezzi; Aliakbar Dariush; Tauanne Dias Amarante; Dan Reshef; Nikaoly Ciriaco; Elena Martinez-Saez; Vicente Peg; Santiago Ramon y Cajal; Javier Cortes; George Vassiliou; Gad Getz; Serena Nik-Zainal; Muhammed Murtaza; Nir Friedman; Florian Markowetz; Joan Seoane; Carlos Caldas

doi:10.1016/j.celrep.2019.04.098

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Leticia De Mattos-Arruda
, Stephen John Sammut
, Edith M. Ross
, Rachael Bashford-Rogers
, Erez Greenstein
, Havell Markus
, Sandro Morganella
, Yvonne Teng
, Yosef Maruvka
, Bernard Pereira
, Oscar M. Rueda
, Suet Feung Chin
, Tania Contente-Cuomo
, Regina Mayor
, Alexandra Arias
, H. Raza Ali
, Wei Cope
, Daniel Tiezzi
, Aliakbar Dariush
, Tauanne Dias Amarante

Dan Reshef, Nikaoly Ciriaco, Elena Martinez-Saez, Vicente Peg, Santiago Ramon y Cajal, Javier Cortes, George Vassiliou, Gad Getz, Serena Nik-Zainal, Muhammed Murtaza, Nir Friedman, Florian Markowetz, Joan Seoane, Carlos Caldas

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

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.

Original language	English
Pages (from-to)	2690-2708.e10
Journal	Cell Reports
Volume	27
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2019.04.098
State	Published - 28 May 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 The Authors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

breast cancer
clade mutations
genomic landscapes
immune landscapes
immunoediting
metastases
metastatic phylogenies
private mutations
stem mutations
TCR repertoire

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10.1016/j.celrep.2019.04.098

Cite this

De Mattos-Arruda, L., Sammut, S. J., Ross, E. M., Bashford-Rogers, R., Greenstein, E., Markus, H., Morganella, S., Teng, Y., Maruvka, Y., Pereira, B., Rueda, O. M., Chin, S. F., Contente-Cuomo, T., Mayor, R., Arias, A., Ali, H. R., Cope, W., Tiezzi, D., Dariush, A., ... Caldas, C. (2019). The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer. Cell Reports, 27(9), 2690-2708.e10. https://doi.org/10.1016/j.celrep.2019.04.098

@article{00553cf4549c482ba25b5ae8d23eb4f7,

title = "The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer",

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.",

keywords = "breast cancer, clade mutations, genomic landscapes, immune landscapes, immunoediting, metastases, metastatic phylogenies, private mutations, stem mutations, TCR repertoire",

author = "\{De Mattos-Arruda\}, Leticia and Sammut, \{Stephen John\} and Ross, \{Edith M.\} and Rachael Bashford-Rogers and Erez Greenstein and Havell Markus and Sandro Morganella and Yvonne Teng and Yosef Maruvka and Bernard Pereira and Rueda, \{Oscar M.\} and Chin, \{Suet Feung\} and Tania Contente-Cuomo and Regina Mayor and Alexandra Arias and Ali, \{H. Raza\} and Wei Cope and Daniel Tiezzi and Aliakbar Dariush and \{Dias Amarante\}, Tauanne and Dan Reshef and Nikaoly Ciriaco and Elena Martinez-Saez and Vicente Peg and \{Ramon y Cajal\}, Santiago and Javier Cortes and George Vassiliou and Gad Getz and Serena Nik-Zainal and Muhammed Murtaza and Nir Friedman and Florian Markowetz and Joan Seoane and Carlos Caldas",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = may,

day = "28",

doi = "10.1016/j.celrep.2019.04.098",

language = "אנגלית",

volume = "27",

pages = "2690--2708.e10",

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De Mattos-Arruda, L, Sammut, SJ, Ross, EM, Bashford-Rogers, R, Greenstein, E, Markus, H, Morganella, S, Teng, Y, Maruvka, Y, Pereira, B, Rueda, OM, Chin, SF, 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 2019, 'The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer', Cell Reports, vol. 27, no. 9, pp. 2690-2708.e10. https://doi.org/10.1016/j.celrep.2019.04.098

TY - JOUR

T1 - The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

AU - De Mattos-Arruda, Leticia

AU - Sammut, Stephen John

AU - Ross, Edith M.

AU - Bashford-Rogers, Rachael

AU - Greenstein, Erez

AU - Markus, Havell

AU - Morganella, Sandro

AU - Teng, Yvonne

AU - Maruvka, Yosef

AU - Pereira, Bernard

AU - Rueda, Oscar M.

AU - Chin, Suet Feung

AU - Contente-Cuomo, Tania

AU - Mayor, Regina

AU - Arias, Alexandra

AU - Ali, H. Raza

AU - Cope, Wei

AU - Tiezzi, Daniel

AU - Dariush, Aliakbar

AU - Dias Amarante, Tauanne

AU - Reshef, Dan

AU - Ciriaco, Nikaoly

AU - Martinez-Saez, Elena

AU - Peg, Vicente

AU - Ramon y Cajal, Santiago

AU - Cortes, Javier

AU - Vassiliou, George

AU - Getz, Gad

AU - Nik-Zainal, Serena

AU - Murtaza, Muhammed

AU - Friedman, Nir

AU - Markowetz, Florian

AU - Seoane, Joan

AU - Caldas, Carlos

PY - 2019/5/28

Y1 - 2019/5/28

N2 - 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.

AB - 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.

KW - breast cancer

KW - clade mutations

KW - genomic landscapes

KW - immune landscapes

KW - immunoediting

KW - metastases

KW - metastatic phylogenies

KW - private mutations

KW - stem mutations

KW - TCR repertoire

UR - https://www.scopus.com/pages/publications/85065906694

U2 - 10.1016/j.celrep.2019.04.098

DO - 10.1016/j.celrep.2019.04.098

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31141692

AN - SCOPUS:85065906694

SN - 2211-1247

VL - 27

SP - 2690-2708.e10

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Abstract

Bibliographical note

UN SDGs

Keywords

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