TY - JOUR
T1 - A feasibility study of returning clinically actionable somatic genomic alterations identified in a research laboratory
AU - Arango, Natalia Paez
AU - Brusco, Lauren
AU - Shaw, Kenna R.Mills
AU - Chen, Ken
AU - Eterovic, Agda Karina
AU - Holla, Vijaykumar
AU - Johnson, Amber
AU - Litzenburger, Beate
AU - Khotskaya, Yekaterina B.
AU - Sanchez, Nora
AU - Bailey, Ann
AU - Zheng, Xiaofeng
AU - Horombe, Chacha
AU - Kopetz, Scott
AU - Farhangfar, Carol J.
AU - Routbort, Mark
AU - Broaddus, Russell
AU - Bernstam, Elmer V.
AU - Mendelsohn, John
AU - Mills, Gordon B.
AU - Meric-Bernstam, Funda
N1 - Publisher Copyright:
© Arango et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - CLIA
KW - Clinical trial
KW - Genomics
KW - Precision medicine
KW - Somatic mutation
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U2 - 10.18632/oncotarget.16018
DO - 10.18632/oncotarget.16018
M3 - Article
C2 - 28415679
AN - SCOPUS:85021296288
SN - 1949-2553
VL - 8
SP - 41806
EP - 41814
JO - Oncotarget
JF - Oncotarget
IS - 26
ER -