title: Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer.
abstract: Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. Cancer Res; 76(22); 6568-76. ©2016 AACR.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. woongyang@skku.edu sangwonum@skku.edu.
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Um
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Je-Gun
authors.initials: JG
authors.lastname: Joung
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jinha
authors.initials: J
authors.lastname: Park
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Hayes
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. woongyang@skku.edu sangwonum@skku.edu.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
mesh_terms: D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis