title: Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation.
abstract: This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular Intelligence, and Response Genetics Inc. For the entire adenocarcinoma cohort, 25% of patients were African Americans; 90% of KRAS mutations were detected in smokers, including current and former smokers; 46% of EGFR and 61% of ALK alterations were detected in never smokers. 99.4% of patients, whose samples were analyzed by next-generation sequencing (NGS), had genetic alterations identified with an average of 10.8 alterations/tumor throughout different tumor subtypes. However, mutations were not mutually exclusive. NGS in this study identified potentially targetable genetic alterations in the majority of patients tested, detected concurrent alterations and provided information on variants of unknown significance at this time but potentially targetable in the future.
authors.affiliation: Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Janani
authors.initials: J
authors.lastname: Vigneswaran
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yi-Hung Carol
authors.initials: YH
authors.lastname: Tan
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Septimiu D
authors.initials: SD
authors.lastname: Murgu
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Won
authors.affiliation: The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA.
authors.forename: Kathryn Alexa
authors.initials: KA
authors.lastname: Patton
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Villaflor
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hoffman
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hensing
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: D Kyle
authors.initials: DK
authors.lastname: Hogarth
authors.affiliation: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Renuka
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Radiology, The University of Chicago, The University of Chicago, Chicago, IL, USA.
authors.forename: Heber
authors.initials: H
authors.lastname: MacMahon
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mueller
authors.affiliation: Cancer Registry, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Simon
authors.affiliation: Department of Surgery, The University of Chicago Medicine and Biologic Sciences, Chicago, IL, USA.
authors.forename: Wickii T
authors.initials: WT
authors.lastname: Vigneswaran
authors.affiliation: Department of Surgery, The University of Chicago Medicine and Biologic Sciences, Chicago, IL, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Wigfield
authors.affiliation: Department of Surgery, The University of Chicago Medicine and Biologic Sciences, Chicago, IL, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Ferguson
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL, USA.
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D057285:Precision Medicine / Q000379:methods*
keywords: genetic testing; genomic alteration; next-generation sequencing; non-small cell lung cancer