A Review of Precision Oncology Knowledgebases for Determining the Clinical Actionability of Genetic Variants

Abstract

The increased availability of tumor genetic testing and targeted cancer therapies contributes to the advancement of precision medicine in the field of oncology. Precision oncology knowledgebases provide a way of organizing clinically relevant genetic information in a way that is easily accessible for both oncologists and patients, facilitating the genetic-based clinical decision making. Many organizations and companies have built precision oncology knowledgebases, intended for multiple users. In general, these knowledgebases offer information on cancer-related genetic variants as well as their associated diagnostic, prognostic, and therapeutic implications, but they often differ in their information curations, designs, and user experiences. It is advisable that oncologists use multiple knowledgebases during their practice to have them complement each other. In the future, convergence toward common standards and formats is needed to ensure that the comprehensive knowledge across all sources can be unified to bring the oncology community closer to the achievement of the goal of precision oncology.

Keywords: actionability; genotype-selective clinical trial; knowledgebase; precision oncology; targeted therapy; tumor genetic testing; variant interpretation.

FIGURE 1

NGS workflow. The processes of ordering, measuring, interpreting, and acting upon clinical NGS information are complex and shared across clinician specialties. This schema outlines the tasks in the typical workflow of precision oncology decision making. Notably this process is iterative, with repetition typically triggered by progression or a prespecified time interval. The brackets illustrate the portion of the workflow that is the subject of this focused review. Traditionally, the test ordering and interpretation steps have clear hand-offs, although roles are becoming increasingly shared e.g., with the advent of molecular tumor boards. While the discussed knowledgebases may have purposes outside of this narrow scope, they also have clear utility in this part of the workflow. Conversely, resources such as COSMIC and dbSNP, which are useful for the laboratory professionals and pathologists’ role in interpreting sequencing data and annotating variants, are deliberately omitted in this mini-review, as they do not typically have a role in this portion of the workflow.