Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial

Ben Tran, Andrew M K Brown, Philippe L. Bedard, Eric Winquist, Glenwood D. Goss, Sebastien J. Hotte, Stephen A. Welch, Hal W. Hirte, Tong Zhang, Lincoln D. Stein, Vincent Ferretti, Stuart Watt, Wei Jiao, Karen Ng, Sangeet Ghai, Patricia Shaw, Teresa Petrocelli, Thomas J. Hudson, Benjamin G. Neel, Nicole OnettoLillian L. Siu, John Douglas Mcpherson, Suzanne Kamel-Reid, Janet E. Dancey

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

The successes of targeted drugs with companion predictive biomarkers and the technological advances in gene sequencing have generated enthusiasm for evaluating personalized cancer medicine strategies using genomic profiling. We assessed the feasibility of incorporating real-time analysis of somatic mutations within exons of 19 genes into patient management. Blood, tumor biopsy and archived tumor samples were collected from 50 patients recruited from four cancer centers. Samples were analyzed using three technologies: targeted exon sequencing using Pacific Biosciences PacBio RS, multiplex somatic mutation genotyping using Sequenom MassARRAY and Sanger sequencing. An expert panel reviewed results prior to reporting to clinicians. A clinical laboratory verified actionable mutations. Fifty patients were recruited. Nineteen actionable mutations were identified in 16 (32%) patients. Across technologies, results were in agreement in 100% of biopsy specimens and 95% of archival specimens. Profiling results from paired archival/biopsy specimens were concordant in 30/34 (88%) patients. We demonstrated that the use of next generation sequencing for real-time genomic profiling in advanced cancer patients is feasible. Additionally, actionable mutations identified in this study were relatively stable between archival and biopsy samples, implying that cancer mutations that are good predictors of drug response may remain constant across clinical stages. What's new? Advances in next generation sequencing (NGS) technologies and cancer genetics have led to considerable enthusiasm for genomic profiling as a tool for the clinical management of cancer. This multi-center clinical trial, which examined different sequencing technologies, demonstrated the feasibility of incorporating NGS technology clinically. Both fresh biopsy and archived samples were found to be suitable for these analyses. If proven cost-effective and clinically beneficial, NGS technologies could result in more effective treatment regimens and improved outcomes for patients.

Original languageEnglish (US)
Pages (from-to)1547-1555
Number of pages9
JournalInternational Journal of Cancer
Volume132
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Keywords

  • cancer genomes
  • molecular profiling
  • next generation sequencing
  • personalized medicine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Tran, B., Brown, A. M. K., Bedard, P. L., Winquist, E., Goss, G. D., Hotte, S. J., Welch, S. A., Hirte, H. W., Zhang, T., Stein, L. D., Ferretti, V., Watt, S., Jiao, W., Ng, K., Ghai, S., Shaw, P., Petrocelli, T., Hudson, T. J., Neel, B. G., ... Dancey, J. E. (2013). Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial. International Journal of Cancer, 132(7), 1547-1555. https://doi.org/10.1002/ijc.27817