L De Mattos-Arruda, S-J Sammut, EM Ross, R Bashford-Rogers, E Greenstein, H Markus, S Morganella, Y Teng, Y Maruvka, B Pereira, OM Rueda, S-F Chin, T Contente-Cuomo, R Mayor, A Arias, HR Ali, W Cope, D Tiezzi, A Dariush, T Dias Amarante, D Reshef, N Ciriaco, E Martinez-Saez, V Peg, S Ramon Y Cajal, J Cortes, G Vassiliou, G Getz, S Nik-Zainal, M Murtaza, N Friedman, F Markowetz, J Seoane, C Caldas
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.