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Cancer discovery DOI:10.1158/2159-8290.CD-11-0184

High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing.

Publication TypeJournal Article
Year of Publication2012
AuthorsWagle, N, Berger, MF, Davis, MJ, Blumenstiel, B, DeFelice, M, Pochanard, P, Ducar, M, Van Hummelen, P, Macconaill, LE, Hahn, WC, Meyerson, M, Gabriel, SB, Garraway, LA
JournalCancer discovery
Date Published2012/01/01

Knowledge of "actionable" somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number alterations that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation of systematic genomic profiling has rarely been achieved beyond limited numbers of oncogene point mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach to detect tumor genomic alterations in formalin-fixed, paraffin-embedded (FFPE) tumor samples. Nearly 400-fold mean sequence coverage was achieved, and single-nucleotide sequence variants, small insertions/deletions, and chromosomal copynumber alterations were detected simultaneously with high accuracy compared with other methods in clinical use. Putatively actionable genomic alterations, including those that predict sensitivity or resistance to established and experimental therapies, were detected in each tumor sample tested. Thus, targeted deep sequencing of clinical tumor material may enable mutation-driven clinical trials and, ultimately, "personalized" cancer treatment.