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 Mills, Funda Meric-Bernstam

Research output: Contribution to journalArticle

28 Citations (Scopus)

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
StatePublished - Jan 1 2015
Externally publishedYes

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Mutation
Neoplasms
Genes
Neoplasm Genes
Research Ethics Committees
Clinical Protocols
Sarcoma
Pancreas
Melanoma
Histology
Genotype
Neoplasm Metastasis
Technology
Kidney
DNA

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., ... Meric-Bernstam, F. (2015). Clinical next generation sequencing to identify actionable aberrations in a phase I program. Oncotarget, 6(24), 20099-20110.

Clinical next generation sequencing to identify actionable aberrations in a phase I program. / 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; Meric-Bernstam, Funda.

In: Oncotarget, Vol. 6, No. 24, 01.01.2015, p. 20099-20110.

Research output: Contribution to journalArticle

Boland, GM, Piha-Paul, SA, Subbiah, V, Routbort, M, Herbrich, SM, Baggerly, K, Patel, KP, Brusco, L, Horombe, C, Naing, A, Fu, S, Hong, DS, Janku, F, Johnson, A, Broaddus, R, Luthra, R, Shaw, K, Mendelsohn, J, Mills, G & Meric-Bernstam, F 2015, 'Clinical next generation sequencing to identify actionable aberrations in a phase I program', Oncotarget, vol. 6, no. 24, pp. 20099-20110.
Boland GM, Piha-Paul SA, Subbiah V, Routbort M, Herbrich SM, Baggerly K et al. Clinical next generation sequencing to identify actionable aberrations in a phase I program. Oncotarget. 2015 Jan 1;6(24):20099-20110.
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 ; Meric-Bernstam, Funda. / Clinical next generation sequencing to identify actionable aberrations in a phase I program. In: Oncotarget. 2015 ; Vol. 6, No. 24. pp. 20099-20110.
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AU - Broaddus, Russell

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