title: Feasibility of real time next generation sequencing of cancer genes linked to drug response: results from a clinical trial.
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.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.forename: Andrew M K
authors.initials: AM
authors.lastname: Brown
authors.forename: Philippe L
authors.initials: PL
authors.lastname: Bedard
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Glenwood D
authors.initials: GD
authors.lastname: Goss
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Welch
authors.forename: Hal W
authors.initials: HW
authors.lastname: Hirte
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Lincoln D
authors.initials: LD
authors.lastname: Stein
authors.forename: Vincent
authors.initials: V
authors.lastname: Ferretti
authors.forename: Stuart
authors.initials: S
authors.lastname: Watt
authors.forename: Wei
authors.initials: W
authors.lastname: Jiao
authors.forename: Karen
authors.initials: K
authors.lastname: Ng
authors.forename: Sangeet
authors.initials: S
authors.lastname: Ghai
authors.forename: Patricia
authors.initials: P
authors.lastname: Shaw
authors.forename: Teresa
authors.initials: T
authors.lastname: Petrocelli
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.forename: Nicole
authors.initials: N
authors.lastname: Onetto
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: John D
authors.initials: JD
authors.lastname: McPherson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Janet E
authors.initials: JE
authors.lastname: Dancey
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D019295:Computational Biology; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D052138:Genes, Neoplasm / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents