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Genomics Editorial Genomics and Precision Cancer Medicine Senthilkumar Damodaran,MD 1 and Sameek Roychowdhury, MD, PhD 1,2,3 1. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, US; 2. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, US; 3. Department of Pharmacology, The Ohio State University, Columbus, Ohio, US Abstract This editorial reports on the abstract “Genomics and Precision Cancer Medicine” presented at the American Society of Clinical Oncology Annual Congress, Chicago, Illinois, US, June 2015. Keywords Genomics, precision cancer, next-generation sequencing Disclosure: Senthilkumar Damodaran, MD, has no disclosures in relation to this article. Sameek Roychowdhury, MD, PhD, receives funding from Novartis and Ariad Pharmaceuticals for conduct of clinical trials. There are no publication fees associated with this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: September 3, 2015 Published Online: November 10, 2015 Citation: Oncology & Hematology Review, 2015;11(2):145–6 Correspondence: Sameek Roychowdhury, MD, PhD, Assistant Professor, Division of Medical Oncology, Departments of Internal Medicine and Pharmacology, Comprehensive Cancer Center, The Ohio State University, 460 West 12th Avenue, Room 508, Columbus, OH 43210, US. E: firstname.lastname@example.org Support: Senthilkumar Damodaran, MD, is supported by the American Society of Clinical Oncology Young Investigator Award; Sameek Roychowdhury, MD, PhD, is supported by the American Cancer Society (MRSG-12-194-01-TBG), the Prostate Cancer Foundation, NHGRI UM1HG006508-01A1, Fore Cancer Research, American Lung Association, and Pelotonia. Sameek Roychowdhury, MD, PhD, has an immediate family member who owns stock in Johnson & Johnson. Advancing technology has led to the successful utilization of next- generation sequencing (NGS) for assessing cancer susceptibility, diagnosis, prognosis, and treatment. 1,2 Currently, matching therapies that target single-nucleotide variations, gene fusions, or copy number variations are approved for clinical use across various tumors. However, clinical application of genomic testing presents some potential challenges, including consent, tissue acquisition, cost, interpretation, privacy, and access to new therapies. While whole exome and whole transcriptome sequencing offer a more comprehensive and unbiased approach, their clinical applicability is limited at present as only a fraction of the cancer genes are actionable. Moreover, they are expensive and time consuming. Consequently, targeted gene capture panels are widely employed both by academic institutions and by commercial vendors for clinical utilization. Targeted gene panels employ select cancer genes that have therapeutic relevance and have been biologically well characterized. These panels have shorter turnaround time, are cost-effective, and are amenable to meet standards for clinical testing such as Clinical Laboratory Improvement Amendments (CLIA) certification and College of American Pathologists (CAP) accreditation. Although cancer gene panels are preferred for clinical use, since they test for select genes they may miss novel genomic alterations. Thus, unbiased strategies such as whole exome and whole transcriptome sequencing are employed in the research setting and present Tou ch MEd ica l MEdia opportunities for discovery. 3,4 As technology and cost improve, we anticipate more widespread utilization of these unbiased sequencing approaches. While DNA sequencing is frequently employed, we anticipate RNA sequencing (RNAseq) to play a more active more role in future. RNASeq can provide data on gene expression, mutations, fusions, splicing, and noncoding RNAs, such as microRNAs. However, cost and time limitations preclude their clinical utilization. Targeted RNAseq approaches could serve as a viable alternative and studies have successfully employed them in cancer care. 5,6 Thus, a combination of targeted DNA and RNA sequencing approaches can provide information on clinically pertinent genomic alterations at a fraction of cost of whole exome and whole transcriptome approaches. Beyond cancer genomic testing methods, there are several challenges for precision cancer medicine that are being actively addressed: clinical interpretation of results, molecular eligibility for trials, and reimbursement. While the goal is to detect oncogenic driver mutations because they confer a growth advantage and represent potential targets for therapy, it is often challenging to separate drivers from the many passenger mutations whose clinical relevance is often unclear. Also, more than one driver mutation can be identified and their clinical significance can be hard to discern. Prediction of action ability based on gain-of-function mutations in commonly observed domains (e.g., kinase), while useful, could be misleading as activating mutations in nonkinase domains are 145