The next steps in next-gen sequencing of cancer genomes
D. Neil Hayes, William Y. Kim
D. Neil Hayes, William Y. Kim
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(2):462-468. https://doi.org/10.1172/JCI68339.
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The next steps in next-gen sequencing of cancer genomes

Abstract

The necessary infrastructure to carry out genomics-driven oncology is now widely available and has resulted in the exponential increase in characterized cancer genomes. While a subset of genomic alterations is clinically actionable, the majority of somatic events remain classified as variants of unknown significance and will require functional characterization. A careful cataloging of the genomic alterations and their response to therapeutic intervention should allow the compilation of an “actionability atlas” and the creation of a genomic taxonomy stratified by tumor type and oncogenic pathway activation. The next phase of genomic medicine will therefore require talented bioinformaticians, genomic navigators, and multidisciplinary approaches to decode complex cancer genomes and guide potential therapy. Equally important will be the ethical and interpretable return of results to practicing oncologists. Finally, the integration of genomics into clinical trials is likely to speed the development of predictive biomarkers of response to targeted therapy as well as define pathways to acquired resistance.

Authors

D. Neil Hayes, William Y. Kim

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Figure 1

Genomics-based oncology workflow and integration of an actionability atlas.

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Genomics-based oncology workflow and integration of an actionability atl...
The sequencing of cancer genomes requires coordinated efforts and constant modification. Patients are consented to access archival tumor tissue or fresh tumor tissue obtained from a new biopsy. Genomic profiles are generated by next-gen sequencing of tumor and normal (germline) tissues and are discussed at MTBs. The decision to report variants back to the patient and physician is made by consensus at the MTB in part based on a categorization of genes predetermined by an independent panel of clinical experts (the Clinical Committee for Genomic Research [CCGR]). Potential outcomes of the reporting of an actionable variant include: enrollment in a clinical trial, off-label use of a current FDA-approved agent, or continued SOC treatment. Systematic cataloging of outcomes into a proposed actionability atlas should aid future decision making.