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

Genevieve M. Boland, Sarina A. Piha-Paul, Vivek Subbiah, Mark Routbort, Shelley M. Herbrich, Keith Baggerly, Keyur P. Patel, Lauren Brusco, Chacha Horombe, Aung Naing, Siqing Fu, David S. Hong, Filip Janku, Amber Johnson, Russell Broaddus, Raja Luthra, Kenna Shaw, John Mendelsohn, Gordon B. Mills, Funda Meric-Bernstam

    Research output: Contribution to journalArticle

    30 Scopus citations

    Abstract

    Purpose: 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.

    Original languageEnglish (US)
    Pages (from-to)20099-20110
    Number of pages12
    JournalOncotarget
    Volume6
    Issue number24
    DOIs
    StatePublished - Jan 1 2015

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    Keywords

    • Actionable genes
    • Genomic sequencing

    ASJC Scopus subject areas

    • Oncology

    Cite this

    Boland, G. M., Piha-Paul, S. A., Subbiah, V., Routbort, M., Herbrich, S. M., Baggerly, K., Patel, K. P., Brusco, L., Horombe, C., Naing, A., Fu, S., Hong, D. S., Janku, F., Johnson, A., Broaddus, R., Luthra, R., Shaw, K., Mendelsohn, J., Mills, G. B., & Meric-Bernstam, F. (2015). Clinical next generation sequencing to identify actionable aberrations in a phase I program. Oncotarget, 6(24), 20099-20110. https://doi.org/10.18632/oncotarget.4040