Abstract:
UNLABELLED: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. SIGNIFICANCE:Despite the rapid proliferation of targeted therapeutic agents, systematic methods to profile clinically relevant tumor genomic alterations remain underdeveloped. We describe a sequencingbased approach to identifying genomic alterations in FFPE tumor samples. These studies affirm the feasibility and clinical utility of targeted sequencing in the oncology arena and provide a foundation for genomics-based stratification of cancer patients.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Wagle 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 LAdoi
10.1158/2159-8290.CD-11-0184subject
Has Abstractpub_date
2012-01-01 00:00:00pages
82-93issue
1eissn
2159-8274issn
2159-8290pii
2159-8290.CD-11-0184journal_volume
2pub_type
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