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The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.


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.

SUBMITTER: De Mattos-Arruda L 

PROVIDER: S-EPMC6546974 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.

De Mattos-Arruda Leticia L   Sammut Stephen-John SJ   Ross Edith M EM   Bashford-Rogers Rachael R   Greenstein Erez E   Markus Havell H   Morganella Sandro S   Teng Yvonne Y   Maruvka Yosef Y   Pereira Bernard B   Rueda Oscar M OM   Chin Suet-Feung SF   Contente-Cuomo Tania T   Mayor Regina R   Arias Alexandra A   Ali H Raza HR   Cope Wei W   Tiezzi Daniel D   Dariush Aliakbar A   Dias Amarante Tauanne T   Reshef Dan D   Ciriaco Nikaoly N   Martinez-Saez Elena E   Peg Vicente V   Ramon Y Cajal Santiago S   Cortes Javier J   Vassiliou George G   Getz Gad G   Nik-Zainal Serena S   Murtaza Muhammed M   Friedman Nir N   Markowetz Florian F   Seoane Joan J   Caldas Carlos C  

Cell reports 20190501 9


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  ...[more]

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