b'Section 4: Genetic analysis technologies to support cancer research Introduction set of mutations or genes needs to be analyzed in a large number Cancer is a disease mediated by genetic alterations, and asof samples with minimal effort, individual TaqMan Assays may be such, tools that can analyze the genome are instrumental inused for detecting these sequences. understanding the mechanisms that lead to cancer, detectingImportantly, these approaches and technologies are cancerous cells, and providing avenues for research oncomplementary to each other. For example, a researcher might cancer treatments. The Human Genome Project resultedstart with a discovery-based approach to catalog the mutations in the development of many tools that generated sequencecommonly found in a tumor, then focus on those mutations by information and used that sequence information to understandconfirmatory Sanger sequencing in more samples, and finally human health and disease, including cancer. Thermo Fisherdesign a TaqMan probe to the mutation(s) that can be used to Scientific has been at the forefront of the developmentstratify patients for a research program. Our solutions continuum of these tools and offers a broad portfolio of solutions inis meant to ease the research path from discovery to insight.cancer research. In this section, we give a brief overview of the technologies in our The portfolio of solutions from Thermo Fisher can be thought ofcontinuum and how they could be used for cancer research. The as a continuum that gives researchers options at every stage offlexibility of these solutions is vast, and can be easily adapted to their research journey, based on the types of questions beinginvestigate the research questions being asked.asked (Figure 1). For example, some investigators might be interested in discovery-based research, using unbiased queriesMicroarray methods and toolsspanning the entire genome to uncover new sequences orWhen a normal cell goes down a path that ultimately ends in a relationships between genes. These types of experiments arecancerous cell, it acquires many mutations that may range from facilitated by Ion AmpliSeq next-generation sequencing (NGS)single-nucleotide changes and small indels to copy number workflows or by Applied Biosystems microarray solutions. Oncechanges and large chromosomal rearrangements. One way a set of sequences of interest is decided, investigators mightto characterize these genomic changes is to use high-density move to a focus-based model, where these selected sequencesDNA microarrays. For these analyses, hundreds of thousands of are analyzed in medium-throughput analyses such as Sangerprobes tiled across the genome are arrayed onto a single chip. sequencing to validate, confirm, and focus on a defined regionSample hybridization to these arrays can determine which across many samples; or Applied Biosystems TaqMan panels to focus on sets containing many genes. Finally, if a very specific Discovery Focus DetectionDiscover new sequences Conrmation of new sequences Analysis of specic sequencesUnbiased queries Analysis of sequence sets of interest Presence/absence testingWhole-genome or transcriptome analysisIon AmpliSeq Transcriptome PanelSanger sequencing by capillary electrophoresisIndividual TaqMan Gene Expression Assays Clariom MicroarraysOpenArray predesigned and custom panelsIndividual genotyping assays Axiom Genotyping ArraysTaqMan exible and custom plate panelsCustom TaqMan Assays Precision Medicine ArraysAbsolute Q Liquid Biopsy Digital PCR AssaysAxiom PharmacoFocus ArraysFigure 1. The genetic analysis continuum. In oncology research, the tools and techniques used depend on the question being asked, the scale of the data that need to be analyzed, and the logistical needs of the investigator. Applied Biosystems genetic analysis systems fall into a continuum, from very large-scale discovery-based research to medium-scale focused research to very targeted detection of specific genes and mutations.Contents 14'