With the advent of next-generation sequencing (NGS), we have the promise of a complete genetic description of patient tumors to optimally direct therapy. Of hundreds to thousands of somatic mutations that exist in each cancer genome, a large number are unique and nonrecurrent variants. Prioritizing and annotating genetic variants identified via NGS technologies remains a major challenge. Some variants occur in tumor genes that have well-established biological and clinical relevance and are putative targets of therapy. However, most variants have limited evidence as predictive markers or are still of unknown significance. Furthermore, how to prioritize therapy when multiple potentially targetable aberrations and/or coexisting resistance mechanisms are identified in a patient’s tumor still remains largely a heuristic task. In this context, there is a growing need for the biomedical research community to have access to curated and up-to-date cancer pharmacogenomic associations. In addition, the community needs to remain cognizant of the potential consequences of misuse or overinterpretation of genomic data. Herein, I describe a systematic framework for variant annotation and prioritization and propose a structured molecular pathology report using standardized terminology in order to best inform oncology clinical practice.
