Identification of Genomic Somatic Variants in Cancer: From Discovery to Actionability

The perfect method to discover and validate actionable somatic variants in cancer has not yet been developed, yet significant progress has been made toward this goal. There have been huge increases in the throughput and cost of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing technologies that have led to the burgeoning possibility of using sequencing data in clinical settings. Discovery of somatic mutations is relatively simple and has been improved recently due to laboratory methods optimization, bioinformatics algorithms development, and the expansion of various databases of population genomic information. Tiered systems of evidence evaluation are currently being used to classify genomic variants for clinicians to more rapidly and accurately determine actionability of these aberrations. These efforts are complicated by the intricacies of communicating sequencing results to physicians and supporting its biological relevance, emphasizing the need for increasing education of clinicians and administrators, and the ongoing development of ethical standards for dealing with incidental results. This chapter will focus on general aspects of DNA and RNA tumor sequencing technologies, data analysis and interpretation, assessment of biological and clinical relevance of genomic aberrations, ethical aspects of germline sequencing, and how these factors impact cancer personalized care.