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:https://doi.org/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 AmaranteDan 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

Weizmann Institute of Science

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

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
Number of pages	29
Journal	Cell Reports
Volume	27
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2019.04.098
State	Published - 28 May 2019

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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https://doi.org/10.1016/j.celrep.2019.04.098License: CC BY

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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. https://doi.org/10.1016/j.celrep.2019.04.098

@article{ec35f0fe44fa4bfd90c563265b574b85,

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.",

author = "{De Mattos-Arruda}, Leticia and Stephen-John Sammut 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 Suet-Feung Chin and Tania Contente-Cuomo and Regina Mayor and Alexandra Arias and Ali, {H. Raza} and Wei Cope and Daniel Tiezzi and Aliakbar Dariush and Amarante, {Tauanne Dias} 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 = "This work was supported by Cancer Research UK. L.D.M.A. was partly funded by Asociaci{\'o}n Espa{\~n}ola contra el C{\'a}ncer. The authors acknowledge Asociaci{\'o}n Espa{\~n}ola contra el C{\'a}ncer, Cellex foundation, and the clinical team at the Breast Cancer Unit of Vall d{\textquoteright}Hebron University Hospital/Institute of Oncology. We are very grateful to the 10 women and their families who donated the autopsy and tumor samples with linked clinical data.",

year = "2019",

month = may,

day = "28",

doi = "https://doi.org/10.1016/j.celrep.2019.04.098",

language = "الإنجليزيّة",

volume = "27",

pages = "2690--2708",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "9",

}

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, Amarante, TD, 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. 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 - Amarante, Tauanne Dias

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

N1 - This work was supported by Cancer Research UK. L.D.M.A. was partly funded by Asociación Española contra el Cáncer. The authors acknowledge Asociación Española contra el Cáncer, Cellex foundation, and the clinical team at the Breast Cancer Unit of Vall d’Hebron University Hospital/Institute of Oncology. We are very grateful to the 10 women and their families who donated the autopsy and tumor samples with linked clinical data.

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.

U2 - https://doi.org/10.1016/j.celrep.2019.04.098

DO - https://doi.org/10.1016/j.celrep.2019.04.098

M3 - مقالة

SN - 2211-1247

VL - 27

SP - 2690

EP - 2708

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Abstract

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