Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine.
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.
Dias-Santagata
Dora
D
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ddiassantagata@partners.org
Akhavanfard
Sara
S
David
Serena S
SS
Vernovsky
Kathy
K
Kuhlmann
Georgiana
G
Boisvert
Susan L
SL
Stubbs
Hannah
H
McDermott
Ultan
U
Settleman
Jeffrey
J
Kwak
Eunice L
EL
Clark
Jeffrey W
JW
Isakoff
Steven J
SJ
Sequist
Lecia V
LV
Engelman
Jeffrey A
JA
Lynch
Thomas J
TJ
Haber
Daniel A
DA
Louis
David N
DN
Ellisen
Leif W
LW
Borger
Darrell R
DR
Iafrate
A John
AJ
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*