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The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.

Published version
Peer-reviewed

Change log

Authors

De Mattos-Arruda, Leticia 
Sammut, Stephen-John 
Ross, Edith M 
Bashford-Rogers, Rachael  ORCID logo  https://orcid.org/0000-0002-6838-0711
Greenstein, Erez 

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.

Description

Keywords

TCR repertoire, breast cancer, clade mutations, genomic landscapes, immune landscapes, immunoediting, metastases, metastatic phylogenies, private mutations, stem mutations, Biomarkers, Tumor, Breast Neoplasms, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomics, Humans, Loss of Heterozygosity, Mutation, Neoplasm Metastasis, Tumor Microenvironment, Exome Sequencing

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

27

Publisher

Elsevier BV
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research UK (unknown)
Cancer Research Uk (None)
Cancer Research UK (unknown)
European Commission (260791)
Cancer Research UK (60098573)
Cancer Research UK (unknown)
Cancer Research UK (CB4140)
Academy of Medical Sciences (ALI 01/08/14)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (660060)
Cancer Research Uk (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
European Commission FP7 Network of Excellence (NoE) (260791)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
Cancer Research UK (C14303/A17197)
Cancer Research UK (19274)
Medical Research Council (MC_PC_12009)
Cancer Research UK (C9545/A29580_do not transfer)
Cancer Research UK (25815)
European Research Council (694620)
Cancer Research UK (23015)
Cancer Research UK (16942)
Cancer Research UK (19274)
CRUK.