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Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.
Miao, Diana; Margolis, Claire A; Vokes, Natalie I; Liu, David; Taylor-Weiner, Amaro; Wankowicz, Stephanie M; Adeegbe, Dennis; Keliher, Daniel; Schilling, Bastian; Tracy, Adam; Manos, Michael; Chau, Nicole G; Hanna, Glenn J; Polak, Paz; Rodig, Scott J; Signoretti, Sabina; Sholl, Lynette M; Engelman, Jeffrey A; Getz, Gad; Jänne, Pasi A; Haddad, Robert I; Choueiri, Toni K; Barbie, David A; Haq, Rizwan; Awad, Mark M; Schadendorf, Dirk; Hodi, F Stephen; Bellmunt, Joaquim; Wong, Kwok-Kin; Hammerman, Peter; Van Allen, Eliezer M.
Afiliação
  • Miao D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Margolis CA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Vokes NI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Liu D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Taylor-Weiner A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Wankowicz SM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Adeegbe D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Keliher D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Schilling B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Tracy A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Manos M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Chau NG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hanna GJ; Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, USA.
  • Polak P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Rodig SJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Signoretti S; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
  • Sholl LM; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Engelman JA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Getz G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Jänne PA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Haddad RI; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Barbie DA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Haq R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Awad MM; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Schadendorf D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Hodi FS; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Bellmunt J; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • Wong KK; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hammerman P; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
  • Van Allen EM; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Nat Genet ; 50(9): 1271-1281, 2018 09.
Article em En | MEDLINE | ID: mdl-30150660
ABSTRACT
Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Repetições de Microssatélites / Neoplasias Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Repetições de Microssatélites / Neoplasias Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos