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Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma.
Reuben, Alexandre; Spencer, Christine N; Prieto, Peter A; Gopalakrishnan, Vancheswaran; Reddy, Sangeetha M; Miller, John P; Mao, Xizeng; De Macedo, Mariana Petaccia; Chen, Jiong; Song, Xingzhi; Jiang, Hong; Chen, Pei-Ling; Beird, Hannah C; Garber, Haven R; Roh, Whijae; Wani, Khalida; Chen, Eveline; Haymaker, Cara; Forget, Marie-Andrée; Little, Latasha D; Gumbs, Curtis; Thornton, Rebecca L; Hudgens, Courtney W; Chen, Wei-Shen; Austin-Breneman, Jacob; Sloane, Robert Szczepaniak; Nezi, Luigi; Cogdill, Alexandria P; Bernatchez, Chantale; Roszik, Jason; Hwu, Patrick; Woodman, Scott E; Chin, Lynda; Tawbi, Hussein; Davies, Michael A; Gershenwald, Jeffrey E; Amaria, Rodabe N; Glitza, Isabella C; Diab, Adi; Patel, Sapna P; Hu, Jianhua; Lee, Jeffrey E; Grimm, Elizabeth A; Tetzlaff, Michael T; Lazar, Alexander J; Wistuba, Ignacio I; Clise-Dwyer, Karen; Carter, Brett W; Zhang, Jianhua; Futreal, P Andrew.
Afiliação
  • Reuben A; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Spencer CN; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Prieto PA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Gopalakrishnan V; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Reddy SM; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Miller JP; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Mao X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • De Macedo MP; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Chen J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Song X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Jiang H; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Chen PL; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Beird HC; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Garber HR; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Roh W; Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Wani K; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Chen E; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Haymaker C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Forget MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Little LD; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Gumbs C; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Thornton RL; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Hudgens CW; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Chen WS; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Austin-Breneman J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Sloane RS; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Nezi L; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Cogdill AP; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Bernatchez C; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Roszik J; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Hwu P; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Woodman SE; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Chin L; Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Tawbi H; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Davies MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Gershenwald JE; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Amaria RN; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Glitza IC; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Diab A; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Patel SP; Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Hu J; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Lee JE; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Grimm EA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Tetzlaff MT; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Lazar AJ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Wistuba II; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Clise-Dwyer K; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Carter BW; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Zhang J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
  • Futreal PA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
NPJ Genom Med ; 22017.
Article em En | MEDLINE | ID: mdl-28819565
ABSTRACT
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2017 Tipo de documento: Article