Transitioning Diagnostic Molecular Pathology to the Genomic Era: Cancer Somatic Mutation Panel Testing

Abstract

The ongoing discovery and validation of cancer molecular biomarkers, as well as their use in the design of targeted therapies, is shifting oncology from tissue- and disease-based treatments to molecular target-based protocols. Conventional methods of cancer genotyping (e.g., cytogenetics, FISH, PCR) are often insufficient for efficiently capturing the molecular complexity of the cancer genome, while next-generation sequencing (NGS), which promises to revolutionize the field, still needs several more years of maturation before it is ready for generalized clinical use. To bridge this divide between traditional assays and the coming NGS era, relatively simple multiplexed diagnostic assays have been developed that use existing molecular techniques to provide high-content molecular information in an efficient and cost-effective manner. One example of such an approach is SNaPshot, a robust and highly sensitive tumor genotyping technique whose only major instrumentation requirement is a capillary electrophoresis-automated DNA sequencer. In this chapter, we will use this assay as an example of current methods for high-throughput clinical genotyping during the transition of diagnostic molecular pathology to the genomic era.