title: Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine.
abstract: Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. We developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management.
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ddiassantagata@partners.org
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.forename: Sara
authors.initials: S
authors.lastname: Akhavanfard
authors.forename: Serena S
authors.initials: SS
authors.lastname: David
authors.forename: Kathy
authors.initials: K
authors.lastname: Vernovsky
authors.forename: Georgiana
authors.initials: G
authors.lastname: Kuhlmann
authors.forename: Susan L
authors.initials: SL
authors.lastname: Boisvert
authors.forename: Hannah
authors.initials: H
authors.lastname: Stubbs
authors.forename: Ultan
authors.initials: U
authors.lastname: McDermott
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Settleman
authors.forename: Eunice L
authors.initials: EL
authors.lastname: Kwak
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Isakoff
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Engelman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Leif W
authors.initials: LW
authors.lastname: Ellisen
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Borger
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
mesh_terms: D019411:Clinical Laboratory Techniques / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods*; D005838:Genotype; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D016133:Polymerase Chain Reaction / Q000379:methods; D057285:Precision Medicine / Q000379:methods*