The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
De Mattos-Arruda, Leticia (Vall d'Hebron Institut d'Oncologia)
Sammut, Stephen-John (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Ross, Edith M. (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Bashford-Rogers, Rachael (Department of Medicine. University of Cambridge)
Greenstein, Erez (Weizmann Institute of Science (Israel). Department of Immunology)
Markus, Havell (Mayo Clinic Center for Individualized Medicine)
Morganella, Sandro (Department of Medical Genetics. The Clinical School. University of Cambridge)
Teng, Yvonne (Cancer Molecular Diagnosis Laboratory. NIHR Cambridge Biomedical Research Centre)
Maruvka, Yosef (Massachusetts General Hospital (Boston))
Pereira, Bernard (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Rueda, Oscar M. (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Chin, Suet-Feung (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Contente-Cuomo, Tania (Mayo Clinic Center for Individualized Medicine)
Mayor, Regina (Centro de Investigación Biomédica en Red de Cáncer)
Arias, Alexandra (Vall d'Hebron Institut d'Oncologia)
Ali, H. Raza (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Cope, Wei (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Tiezzi, Daniel (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Dariush, Aliakbar (Institute of Astronomy. University of Cambridge)
Dias Amarante, Tauanne (Department of Medical Genetics. The Clinical School. University of Cambridge)
Reshef, Dan (Weizmann Institute of Science (Israel). Department of Immunology)
Ciriaco, Nikaoly (Hospital Universitari Vall d'Hebron)
Martinez-Saez, Elena (Hospital Universitari Vall d'Hebron)
Peg, Vicente (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ramón y Cajal, Santiago (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cortés, Javier (Vall d'Hebron Institut d'Oncologia)
Vassiliou, George (Wellcome Trust/MRC Cambridge Stem Cell Institute)
Getz, Gad (Massachusetts General Hospital (Boston))
Nik-Zainal, Serena (Department of Medical Genetics. The Clinical School. University of Cambridge)
Murtaza, Muhammed (Mayo Clinic Center for Individualized Medicine)
Friedman, Nir (Weizmann Institute of Science (Israel). Department of Immunology)
Markowetz, Florian (Department of Oncology and Cancer Research UK Cambridge Institute. Li Ka Shing Centre. University of Cambridge)
Seoane Suárez, Joan (Vall d'Hebron Institut d'Oncologia)
Caldas, Carlos (Cancer Research UK Cambridge Cancer Centre (Regne Unit))
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Nreast cancer ; Metastases ; Stem mutations ; Clade mutations ; Private mutations ; Genomic landscapes ; Immune landscapes ; Metastatic phylogenies ; Immunoediting ; TCR repertoire
Publicado en:	Cell reports, Vol. 27 Núm. 9 (28 2019) , p. 2690-2708.e10, ISSN 2211-1247

DOI: 10.1016/j.celrep.2019.04.098
PMID: 31141692

30 p, 7.5 MB

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