The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

Mattos Arruda, Leticia de; Sammut, Stephen-John; Ross, Edith M; Bashford-Rogers, Rachael; Greenstein, Erez; Markus, Havell; Mayor Ferreras, Regina Gabriela; Arias Piñeiro, Alexandra; Ciriaco Cortés, Nikaoly; Martinez Saez, Elena Antima; Peg Camara, Vicente; Ramon y Cajal Agüeras, Santiago; Cortés Castan, Javier; Seoane Suarez, Joan

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.

Keywords

TCR repertoire; Breast cancer; Clade mutations

Bibliographic citation

De Mattos-Arruda L, Sammut S-J, Ross EM, Bashford-Rogers R, Greenstein E, Markus H, et al. The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer. Cell Rep. 2019; 27(9):2690-2708.