| Autor: |
Leticia De Mattos-Arruda, Stephen-John Sammut, Edith M. Ross, Rachael Bashford-Rogers, Erez Greenstein, Havell Markus, Sandro Morganella, Yvonne Teng, Yosef Maruvka, Bernard Pereira, Oscar M. Rueda, Suet-Feung Chin, Tania Contente-Cuomo, Regina Mayor, Alexandra Arias, H. Raza Ali, Wei Cope, Daniel Tiezzi, Aliakbar Dariush, Tauanne Dias Amarante, Dan Reshef, Nikaoly Ciriaco, Elena Martinez-Saez, Vicente Peg, Santiago Ramon y Cajal, Javier Cortes, George Vassiliou, Gad Getz, Serena Nik-Zainal, Muhammed Murtaza, Nir Friedman, Florian Markowetz, Joan Seoane, Carlos Caldas |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 27, Iss 9, Pp 2690-2708.e10 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.04.098 |
| Popis: |
Summary: 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. : De Mattos-Arruda et al. profiled multiple metastases from autopsies of patients with therapy-resistant breast cancer, showing that multi-clonal spreading occurs in a small number of founder events. The analysis characterizes predicted neo-antigen landscapes, tumor microenvironments, and accumulation of HLA LOH. T cell immune responses appear to co-evolve with metastatic cancer genomes. Keywords: breast cancer, metastases, stem mutations, clade mutations, private mutations, genomic landscapes, immune landscapes, metastatic phylogenies, immunoediting, TCR repertoire |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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