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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 publication

DOI

10.1016/j.celrep.2019.04.098

Type

Journal article

Journal

Cell Rep

Publication Date

28/05/2019

Volume

27

Pages

2690 - 2708.e10

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, Whole Exome Sequencing