Your browser doesn't support javascript.
loading
Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer.
Anagnostou, Valsamo; Niknafs, Noushin; Marrone, Kristen; Bruhm, Daniel C; White, James R; Naidoo, Jarushka; Hummelink, Karlijn; Monkhorst, Kim; Lalezari, Ferry; Lanis, Mara; Rosner, Samuel; Reuss, Joshua E; Smith, Kellie N; Adleff, Vilmos; Rodgers, Kristen; Belcaid, Zineb; Rhymee, Lamia; Levy, Benjamin; Feliciano, Josephine; Hann, Christine L; Ettinger, David S; Georgiades, Christos; Verde, Franco; Illei, Peter; Li, Qing Kay; Baras, Alexander S; Gabrielson, Edward; Brock, Malcolm V; Karchin, Rachel; Pardoll, Drew M; Baylin, Stephen B; Brahmer, Julie R; Scharpf, Robert B; Forde, Patrick M; Velculescu, Victor E.
Afiliação
  • Anagnostou V; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. vanagno1@jhmi.edu.
  • Niknafs N; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA. vanagno1@jhmi.edu.
  • Marrone K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Bruhm DC; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • White JR; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Naidoo J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hummelink K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Monkhorst K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lalezari F; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Lanis M; Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, the Netherlands.
  • Rosner S; Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, the Netherlands.
  • Reuss JE; Antoni van Leeuwenhoek Nederlands Kanker Instituut, Amsterdam, the Netherlands.
  • Smith KN; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Adleff V; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rodgers K; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Belcaid Z; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rhymee L; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Levy B; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Feliciano J; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hann CL; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ettinger DS; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Georgiades C; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Verde F; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Illei P; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Li QK; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Baras AS; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Gabrielson E; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Brock MV; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Karchin R; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Pardoll DM; Department of Radiology and Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Baylin SB; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Brahmer JR; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Scharpf RB; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Forde PM; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Velculescu VE; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Cancer ; 1(1): 99-111, 2020 01.
Article em En | MEDLINE | ID: mdl-32984843
ABSTRACT
Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in nonresponding tumors in three immunotherapy treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature and human leukocyte antigen status provided an improved predictor of response to immunotherapy that was independently validated.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos