Handbook of Targeted Cancer Therapy and Immunotherapy

87 Introduction At the turn of the millennium, one of the largest breakthroughs in contemporary med ical science was announced—the majority of the human genome had been sequenced, unveiling a new road map for human biology (1). Over the past two decades, sequencing technolo gies have advanced at a rapid pace, which has had broad implications for the detection and treat ment of human disease (2). The field of oncology has been at the forefront of these developments, considering the relevance of genetics in cancer. High-throughput sequencing, or next-generation sequencing (NGS), has made comprehensive molecular profiling of cancers feasible and has pro foundly changed our understanding of human tumor biology (3). Although NGS was once considered cost-prohibitive and utilized sparingly for research efforts, it is now commonplace in oncology practices (4). This has given rise to the era of precision oncology, which refers to a personalized approach to cancer medicine by using an individual tumor’s molec ular characteristics to guide therapeutic decision-making (5). Rapid identification of alterations in cancer-related genes, which may have diagnostic, prognostic, and/or therapeutic relevance, has revolutionized modern cancer care. In this chapter, we will introduce high-throughput sequencing by reviewing the historical context into the sequencing of the cancer genome, discussing platforms to detect alterations within the genome and transcriptome, how high-throughput sequencing data can be leveraged for the treatment of cancer patients, and challenges with integrating these data into clinical practice. Sequencing the Cancer Genome Shortly after completion of the Human Genome Project, several international efforts were launched to comprehensively profile a diverse set of cancers and to gain insight into tumorigenesis, most notably The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) (6,7). Although many oncogenic drivers/tumor suppressors had previously been identified, it was clear that an understanding of the spectrum of genomic aberrations that drive cancers was imper ative. The vision for the TCGA project, as put forth by the National Institutes of Health (NIH), was ambitious—multiple centers and a vast array of multiomics approaches were utilized to molecu larly profile > 30 different tumor types (8). Methods to acquire these data included RNA sequencing

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