The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Leticia De Mattos‐Arruda(Hebron University), Stephen‐John Sammut(University of Cambridge), Edith Ross(University of Cambridge), Rachael Bashford-Rogers(University of Cambridge), Erez Greenstein(Weizmann Institute of Science), Havell Markus(Translational Genomics Research Institute), Sandro Morganella(University of Cambridge), Yvonne H. F. Teng(NIHR Cambridge Biomedical Research Centre), Yosef E. Maruvka(Broad Institute), Bernard Pereira(University of Cambridge), Oscar M. Rueda(University of Cambridge), Suet‐Feung Chin(University of Cambridge), Tania Contente‐Cuomo(Translational Genomics Research Institute), Regina Mayor(Hebron University), Alexandra Arias(Hebron University), H. Raza Ali(University of Cambridge), Wei Cope(University of Cambridge), Daniel Guimarães Tiezzi(University of Cambridge), Aliakbar Dariush(University of Cambridge), Tauanne Dias Amarante(University of Cambridge), Dan Reshef(Weizmann Institute of Science), Nikaoly Ciriaco(Vall d'Hebron Hospital Universitari), Elena Martínez‐Sáez(Hebron University), Vicente Peg(Hebron University), Santiago Ramón y Cajal(Universitat Autònoma de Barcelona), Javier Cortés(Hebron University), George S. Vassiliou(Wellcome/MRC Cambridge Stem Cell Institute), Gad Getz(Broad Institute), Serena Nik‐Zainal(University of Cambridge), Muhammed Murtaza(Translational Genomics Research Institute), Nir Friedman(Weizmann Institute of Science), Florian Markowetz(University of Cambridge), Joan Seoane(Institució Catalana de Recerca i Estudis Avançats), Carlos Caldas(University of Cambridge)
Cell Reports
May 1, 2019
10.1016/j.celrep.2019.04.098
Cited by 114Open Access
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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.

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