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