A feasibility study of returning clinically actionable somatic genomic alterations identified in a research laboratory

// Natalia Paez Arango 1 , Lauren Brusco 2 , Kenna R. Mills Shaw 2 , Ken Chen 3 , Agda Karina Eterovic 4 , Vijaykumar Holla 2 , Amber Johnson 2 , Beate Litzenburger 2 , Yekaterina B. Khotskaya 2 , Nora Sanchez 2 , Ann Bailey 2 , Xiaofeng Zheng 3 , Chacha Horombe 2 , Scott Kopetz 5 , Carol J. Farhangfar 6 , Mark Routbort 7 , Russell Broaddus 8 , Elmer V. Bernstam 9,10 , John Mendelsohn 2,11 , Gordon B. Mills 2,4 and Funda Meric-Bernstam 1,2,12 1 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA 7 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9 School of Biomedical Informatics, The University of Texas Health Science Center at Houston, TX, USA 10 Division of General Internal Medicine, Medical School, The University of Texas Health Science Center at Houston, TX, USA 11 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 12 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Funda Meric-Bernstam, email: // Keywords : precision medicine, genomics, somatic mutation, CLIA, clinical trial Received : November 09, 2016 Accepted : February 27, 2017 Published : March 08, 2017 Abstract Purpose: Molecular profiling performed in the research setting usually does not benefit the patients that donate their tissues. Through a prospective protocol, we sought to determine the feasibility and utility of performing broad genomic testing in the research laboratory for discovery, and the utility of giving treating physicians access to research data, with the option of validating actionable alterations in the CLIA environment. Experimental design: 1200 patients with advanced cancer underwent characterization of their tumors with high depth hybrid capture sequencing of 201 genes in the research setting. Tumors were also tested in the CLIA laboratory, with a standardized hotspot mutation analysis on an 11, 46 or 50 gene platform. Results: 527 patients (44%) had at least one likely somatic mutation detected in an actionable gene using hotspot testing. With the 201 gene panel, 945 patients (79%) had at least one alteration in a potentially actionable gene that was undetected with the more limited CLIA panel testing. Sixty-four genomic alterations identified on the research panel were subsequently tested using an orthogonal CLIA assay. Of 16 mutations tested in the CLIA environment, 12 (75%) were confirmed. Twenty-five (52%) of 48 copy number alterations were confirmed. Nine (26.5%) of 34 patients with confirmed results received genotype-matched therapy. Seven of these patients were enrolled onto genotype-matched targeted therapy trials. Conclusion: Expanded cancer gene sequencing identifies more actionable genomic alterations. The option of CLIA validating research results can provide alternative targets for personalized cancer therapy.