Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation

// Janani Vigneswaran 1, * , Yi-Hung Carol Tan 2, * , Septimiu D. Murgu 3, * , Brian M. Won 2 , Kathryn Alexa Patton 9 , Victoria M. Villaflor 2 , Philip C. Hoffman 2 , Thomas Hensing 2 , D. Kyle Hogarth 3 , Renuka Malik 4 , Heber MacMahon 5 , Jeffrey Mueller 6 , Cassie A. Simon 7 , Wickii T. Vigneswaran 8 , Christopher H. Wigfield 8 , Mark K. Ferguson 8 , Aliya N. Husain 6 , Everett E. Vokes 2 , Ravi Salgia 10 1 Alpert Medical School, Brown University, Providence, RI, USA 2 Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA 3 Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA 4 Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA 5 Department of Radiology, The University of Chicago, Chicago, IL, USA 6 Department of Pathology, The University of Chicago, Chicago, IL, USA 7 Cancer Registry, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA 8 Department of Surgery, The University of Chicago Medicine and Biologic Sciences, Chicago, IL, USA 9 The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA 10 Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA * These authors have contributed equally to this work Correspondence to: Ravi Salgia, e-mail: rsalgia@coh.org Keywords: non-small cell lung cancer, genetic testing, next-generation sequencing, genomic alteration Received: September 30, 2015 Accepted: January 23, 2016 Published: February 26, 2016 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.