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

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Resum

© 2019 The Authors 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.
Idioma originalEnglish
Pàgines (de-a)2690-2708.e10
RevistaCell Reports
Volum27
DOIs
Estat de la publicacióPublicada - 28 de maig 2019

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