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Feasibility of real time next generation sequencing of cancer genes linked to drug response: Results from a clinical trial |
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| Authors: | 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 Onetto Janet E. Dancey |
| Affiliation: | 1. Department of Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada;2. Department of Medical Oncology, London Health Sciences Centre, London, Canada;3. Division of Medical Oncology, Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada;4. Department of Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada;5. The Department of Cellular and Molecular Biology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada;6. Ontario Institute for Cancer Research, Toronto, Ontario, Canada;7. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada;8. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;9. Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada;10. NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, CanadaB.T., A.M.K.B., L.L.S., J.D.M., S.K.‐R. and J.E.D contributed equally to this work.Tel.: +1‐613‐533‐6430, Fax: +1‐613‐533‐6511 |
| 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. |
| Keywords: | molecular profiling cancer genomes next generation sequencing personalized medicine |