The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

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 AmaranteDan 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

Research output: Contribution to journalArticleResearch

20 Citations (Scopus)

Abstract

© 2019 The Authors 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.
Original languageEnglish
Pages (from-to)2690-2708.e10
JournalCell Reports
Volume27
DOIs
Publication statusPublished - 28 May 2019

Keywords

  • breast cancer
  • clade mutations
  • genomic landscapes
  • immune landscapes
  • immunoediting
  • metastases
  • metastatic phylogenies
  • private mutations
  • stem mutations
  • TCR repertoire

Fingerprint Dive into the research topics of 'The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer'. Together they form a unique fingerprint.

Cite this