Clinical next generation sequencing to identify actionable aberrations in a phase I program

We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at t...

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Bibliographic Details
Published in:Oncotarget 2015-08, Vol.6 (24), p.20099-20110
Main Authors: Boland, Genevieve M, Piha-Paul, Sarina A, Subbiah, Vivek, Routbort, Mark, Herbrich, Shelley M, Baggerly, Keith, Patel, Keyur P, Brusco, Lauren, Horombe, Chacha, Naing, Aung, Fu, Siqing, Hong, David S, Janku, Filip, Johnson, Amber, Broaddus, Russell, Luthra, Raja, Shaw, Kenna, Mendelsohn, John, Mills, Gordon B, Meric-Bernstam, Funda
Format: Article
Language:English
Subjects:
High-Throughput Nucleotide Sequencing - methods
Humans
Mutation
Neoplasms - genetics
Precision Medicine - methods
Research Paper
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Summary:We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. 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). 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. Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.4040