Institutional implementation of clinical tumor profiling on an unselected cancer population

作者：Lynette M. Sholl, T. Khanh, Priyanka Shivdasani, Ethan Cerami, Adrian M. Dubuc, Frank C. Kuo, Elizabeth P. Garcia, Yonghui Jia, Phani K. Davineni, Ryan Abo, Trevor J. Pugh, Paul Van Hummelen, Aaron R. Thorner, Matthew D. Ducar, Alice H. Berger, Mizuki Nishino, Katherine A. Janeway, Alanna J. Church, Marian H. Harris, Lauren L. Ritterhouse, Joshua D. Campbell, Vanesa Rojas‐Rudilla, Azra H. Ligon, Shakti Ramkissoon, James M. Cleary, Ursula A. Matulonis, Geoffrey R. Oxnard, Richard C. Chao, Vanessa Tassell, James G. Christensen, William C. Hahn, Philip W. Kantoff, David J. Kwiatkowski, Bruce E. Johnson, Matthew Meyerson, Levi A. Garraway, Geoffrey I. Shapiro, Barrett J. Rollins, Neal I. Lindeman, Laura E. MacConaill · 发表于：JCI Insight · 年份：2016 · DOI：10.1172/jci.insight.87062 · 被引用次数：452 · 研究领域：Cancer Genomics and Diagnostics、Pancreatic and Hepatic Oncology Research、Lung Cancer Treatments and Mutations

BACKGROUND. Comprehensive genomic profiling of a patient’s cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported. METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested. RESULTS. Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including in AXL and EGFR , associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a “cancer-agnostic” approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where di...