High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing

摘要: Knowledge of “actionable” somatic genomic alterations present in each tumor (e.g., point mutations, small insertions/deletions, and copy-number that direct therapeutic options) should facilitate individualized approaches to cancer treatment. However, clinical implementation systematic profiling has rarely been achieved beyond limited numbers oncogene mutations. To address this challenge, we utilized a targeted, massively parallel sequencing approach detect formalin-fixed, paraffin-embedded (FFPE) samples. Nearly 400-fold mean sequence coverage was achieved, single-nucleotide variants, chromosomal copynumber were detected simultaneously with high accuracy compared other methods use. Putatively actionable alterations, including those predict sensitivity or resistance established experimental therapies, sample tested. Thus, targeted deep material may enable mutation-driven trials and, ultimately, “personalized” treatment. Significance: Despite the rapid proliferation agents, profile clinically relevant remain underdeveloped. We describe sequencing-based identifying FFPE These studies affirm feasibility utility oncology arena provide foundation for genomics-based stratification patients. Cancer Discovery; 2(1) ; 82–93. ©2011 AACR . Read Commentary on article by Corless Spellman, [p. 23][1] This is highlighted In This Issue feature, 1][2] [1]: /lookup/volpage/2/23?iss=1 [2]: /lookup/volpage/2/1?iss=1