The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

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. Th...

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Autores principales: De Mattos-Arruda, Leticia, Sammut, Stephen-John, Ross, Edith M., Bashford-Rogers, Rachael, Greenstein, Erez, Markus, Havell, Morganella, Sandro, Teng, Yvonne, Maruvka, Yosef, Pereira, Bernard, Rueda, Oscar M., Chin, Suet-Feung, Contente-Cuomo, Tania, Mayor, Regina, Arias, Alexandra, Ali, H. Raza, Cope, Wei, Tiezzi, Daniel, Dariush, Aliakbar, Dias Amarante, Tauanne, Reshef, Dan, Ciriaco, Nikaoly, Martinez-Saez, Elena, Peg, Vicente, Ramon y Cajal, Santiago, Cortes, Javier, Vassiliou, George, Getz, Gad, Nik-Zainal, Serena, Murtaza, Muhammed, Friedman, Nir, Markowetz, Florian, Seoane, Joan, Caldas, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546974/
https://www.ncbi.nlm.nih.gov/pubmed/31141692
http://dx.doi.org/10.1016/j.celrep.2019.04.098
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author De Mattos-Arruda, Leticia
Sammut, Stephen-John
Ross, Edith M.
Bashford-Rogers, Rachael
Greenstein, Erez
Markus, Havell
Morganella, Sandro
Teng, Yvonne
Maruvka, Yosef
Pereira, Bernard
Rueda, Oscar M.
Chin, Suet-Feung
Contente-Cuomo, Tania
Mayor, Regina
Arias, Alexandra
Ali, H. Raza
Cope, Wei
Tiezzi, Daniel
Dariush, Aliakbar
Dias Amarante, Tauanne
Reshef, Dan
Ciriaco, Nikaoly
Martinez-Saez, Elena
Peg, Vicente
Ramon y Cajal, Santiago
Cortes, Javier
Vassiliou, George
Getz, Gad
Nik-Zainal, Serena
Murtaza, Muhammed
Friedman, Nir
Markowetz, Florian
Seoane, Joan
Caldas, Carlos
author_facet De Mattos-Arruda, Leticia
Sammut, Stephen-John
Ross, Edith M.
Bashford-Rogers, Rachael
Greenstein, Erez
Markus, Havell
Morganella, Sandro
Teng, Yvonne
Maruvka, Yosef
Pereira, Bernard
Rueda, Oscar M.
Chin, Suet-Feung
Contente-Cuomo, Tania
Mayor, Regina
Arias, Alexandra
Ali, H. Raza
Cope, Wei
Tiezzi, Daniel
Dariush, Aliakbar
Dias Amarante, Tauanne
Reshef, Dan
Ciriaco, Nikaoly
Martinez-Saez, Elena
Peg, Vicente
Ramon y Cajal, Santiago
Cortes, Javier
Vassiliou, George
Getz, Gad
Nik-Zainal, Serena
Murtaza, Muhammed
Friedman, Nir
Markowetz, Florian
Seoane, Joan
Caldas, Carlos
author_sort De Mattos-Arruda, Leticia
collection PubMed
description 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.
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spelling pubmed-65469742019-06-06 The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer De Mattos-Arruda, Leticia Sammut, Stephen-John Ross, Edith M. Bashford-Rogers, Rachael Greenstein, Erez Markus, Havell Morganella, Sandro Teng, Yvonne Maruvka, Yosef Pereira, Bernard Rueda, Oscar M. Chin, Suet-Feung Contente-Cuomo, Tania Mayor, Regina Arias, Alexandra Ali, H. Raza Cope, Wei Tiezzi, Daniel Dariush, Aliakbar Dias Amarante, Tauanne Reshef, Dan Ciriaco, Nikaoly Martinez-Saez, Elena Peg, Vicente Ramon y Cajal, Santiago Cortes, Javier Vassiliou, George Getz, Gad Nik-Zainal, Serena Murtaza, Muhammed Friedman, Nir Markowetz, Florian Seoane, Joan Caldas, Carlos Cell Rep Article 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. Cell Press 2019-05-28 /pmc/articles/PMC6546974/ /pubmed/31141692 http://dx.doi.org/10.1016/j.celrep.2019.04.098 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
De Mattos-Arruda, Leticia
Sammut, Stephen-John
Ross, Edith M.
Bashford-Rogers, Rachael
Greenstein, Erez
Markus, Havell
Morganella, Sandro
Teng, Yvonne
Maruvka, Yosef
Pereira, Bernard
Rueda, Oscar M.
Chin, Suet-Feung
Contente-Cuomo, Tania
Mayor, Regina
Arias, Alexandra
Ali, H. Raza
Cope, Wei
Tiezzi, Daniel
Dariush, Aliakbar
Dias Amarante, Tauanne
Reshef, Dan
Ciriaco, Nikaoly
Martinez-Saez, Elena
Peg, Vicente
Ramon y Cajal, Santiago
Cortes, Javier
Vassiliou, George
Getz, Gad
Nik-Zainal, Serena
Murtaza, Muhammed
Friedman, Nir
Markowetz, Florian
Seoane, Joan
Caldas, Carlos
The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title_full The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title_fullStr The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title_full_unstemmed The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title_short The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
title_sort genomic and immune landscapes of lethal metastatic breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546974/
https://www.ncbi.nlm.nih.gov/pubmed/31141692
http://dx.doi.org/10.1016/j.celrep.2019.04.098
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