N. Paez Arango1, L. Brusco2, K. R. Shaw2, K. Chen3, K. Eterovic4, V. Holla2, A. Johnson2, B. Litzenburger2, Y. B. Khotskaya2, N. Sanchez2, A. Bailey2, X. Zheng4, C. Horombe2, S. Kopetz5, C. Farhangfar6, M. Routbort7, R. Broaddus8, E. S. Bernstam9, J. Mendelsohn2, G. B. Mills2,4, F. Meric-Bernstam1,2,10 1University Of Texas MD Anderson Cancer Center,Department Of Surgical Oncology,Houston, TX, USA 2Univerisity Of Texas MD Anderson Cancer Center,Khalifa Institute For Personalized Cancer Therapy,Houston, TX, USA 3University Of Texas MD Anderson Cancer Center,Department Of Bioinformatics And Computational Biology,Houston, TX, USA 4University Of Texas MD Anderson Cancer Center,Department Of Systems Biology,Houston, TX, USA 5University Of Texas MD Anderson Cancer Center,Gastrointestinal Medical Oncology,Houston, TX, USA 6Carolinas Healthcare System,Levine Cancer Institute,Charlotte, NC, USA 7University Of Texas MD Anderson Cancer Center,Department Of Hematopathology,Houston, TX, USA 8University Of Texas MD Anderson Cancer Center,Department Of Pathology,Houston, TX, USA 9University Of Texas Health Science Center At Houston,School Of Biomedical Informatics,Houston, TX, USA 10University Of Texas MD Anderson Cancer Center,Department Of Investigational Cancer Therapeutics,Houston, TX, USA
Introduction: The increasing availability of molecular therapeutics targeting specific genomic alterations has led to an increased interest in the use of next-generation sequencing to help identify patients that could potentially benefit from targeted clinical trials and personalized cancer therapies. Expanding the number of genes and incorporating copy number testing could potentially aid in identifying a higher number of genomic alterations in clinically actionable genes, and thus identify a greater number of patients that could likely benefit from targeted therapy. The purpose of this study was to look at patients who underwent routine genomic profiling under standard hotspot analysis and then using a deep targeted sequencing platform in the research setting, assess the added value to having a more comprehensive genomic test.
Methods: 1200 patients with advanced cancer underwent routine tumor profiling for characterization of common mutations on an 11, 46, or 50 gene hotspot sequencing platform in the Clinical Laboratory Improvement Amendments (CLIA) certified environment, as well as on 201 gene deep targeted sequencing platform in the research setting. 120 genes were considered actionable based on their potential to be targeted with available therapies.
Results:Five hundred and twenty eight patients (44%) had at least one mutation detected in a potentially actionable gene using standard hotspot genomic testing under a limited gene panel, with a total of 644 mutations detected. Under deep targeted sequencing in the research setting, we identified 686 patients (57%) that had at least one somatic mutation in a potentially actionable gene that was previously undetected in the standard testing, with a total of 2448 newly identified mutations. Additionally, we detected 654 (55%) patients with at least one potential copy number variation, with a total of 2784 potential copy number variations identified. A grand total of 5232 alterations in potentially actionable genes were found that would have been otherwise undetected (see table).
Conclusion:Expanded cancer gene sequencing for profiling somatic mutations identifies a greater number of alterations in potentially actionable genes that could have a clinical significance, allowing for the identification of an increased number of targets for personalized cancer therapies.
