Research Papers:

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

Janani Vigneswaran _, Yi-Hung Carol Tan, Septimiu D. Murgu, Brian M. Won, Kathryn Alexa Patton, Victoria M. Villaflor, Philip C. Hoffman, Thomas Hensing, Kyle D. Hogarth, Renuka Malik, Heber MacMahon, Jeffrey Mueller, Cassie A. Simon, Wickii T. Vigneswaran, Christopher H. Wigfield, Mark K. Ferguson, Aliya N. Husain, Everett E. Vokes and Ravi Salgia

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Oncotarget. 2016; 7:18876-18886. https://doi.org/10.18632/oncotarget.7739

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Janani Vigneswaran1,*, Yi-Hung Carol Tan2,*, Septimiu D. Murgu3,*, Brian M. Won2, Kathryn Alexa Patton9, Victoria M. Villaflor2, Philip C. Hoffman2, Thomas Hensing2, D. Kyle Hogarth3, Renuka Malik4, Heber MacMahon5, Jeffrey Mueller6, Cassie A. Simon7, Wickii T. Vigneswaran8, Christopher H. Wigfield8, Mark K. Ferguson8, Aliya N. Husain6, Everett E. Vokes2, Ravi Salgia10

1Alpert Medical School, Brown University, Providence, RI, USA

2Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA

3Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA

4Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA

5Department of Radiology, The University of Chicago, Chicago, IL, USA

6Department of Pathology, The University of Chicago, Chicago, IL, USA

7Cancer Registry, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA

8Department of Surgery, The University of Chicago Medicine and Biologic Sciences, Chicago, IL, USA

9The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, NH, USA

10Department 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


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.

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