Clinical application of DNA sequencing: Sanger and next-generation platforms

Abstract

Cancer is a disease of the genome and all cancers arise due to alterations in DNA that allow the cell to override the checks and balances that are essential for controlled growth and differentiation. To date, the clinical management of cancer has largely been guided by knowing the tissue of origin and histopathological appearance of the tumor with only a limited use of measurement of altered protein expression and DNA aberrations. Sanger/capillary sequencing is the clinical mainstay for DNA sequencing but suffers from low detection sensitivity in heterogeneous tumor cell populations and limited throughput. Next-generation sequencing platforms enable massively parallel analysis of DNA generating millions of template sequences simultaneously. This heralds a new era of cancer genome investigation whereby the determination of the full spectrum of molecular changes in a tumor is now possible on a large scale. Rapid DNA analysis to derive a molecular profile of a tumour with respect to somatic mutations can be used to match specific drugs or treatments to the individual patient. This personalized medicine approach brings the hope that by understanding the specific underlying genetic alterations driving malignant growth of a tumor, treatment regimens specifically targeting the aberrant gene will be possible improving treatment outcomes.