Clinical next generation sequencing to identify actionable aberrations in a phase I program
Piha-Paul, Sarina A.
Herbrich, Shelley M.
Patel, Keyur P.
Hong, David S.
Mills, Gordon B.
Meric-Bernstam, FundaNote: Order does not necessarily reflect citation order of authors.
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CitationBoland, G. M., S. A. Piha-Paul, V. Subbiah, M. Routbort, S. M. Herbrich, K. Baggerly, K. P. Patel, et al. 2015. “Clinical next generation sequencing to identify actionable aberrations in a phase I program.” Oncotarget 6 (24): 20099-20110.
AbstractPurpose We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. Methods: We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at the MD Anderson Cancer Center. Archival tumor DNA was tested for 740 hotspot mutations in 46 genes (Ampli-Seq Cancer Panel; Life Technologies, CA). Results: Of the 500 patients, 362 had at least one reported mutation/variant. The most common likely somatic mutations were within TP53 (36%), KRAS (11%), and PIK3CA (9%) genes. Sarcoma (20%) and kidney (30%) had the lowest proportion of likely somatic mutations detected, while pancreas (100%), colorectal (89%), melanoma (86%), and endometrial (75%) had the highest. There was high concordance in 62 patients with paired primary tumors and metastases analyzed. 151 (30%) patients had alterations in potentially actionable genes. 37 tumor types were enrolled; both rare actionable mutations in common tumor types and actionable mutations in rare tumor types were identified. Conclusion: Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23993547
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