Handbook of Targeted Cancer Therapy and Immunotherapy

90 Several NGS platforms have emerged, which may be encountered by oncologists, including commercially available/adapted platforms, institutionally developed plat forms, and research-based platforms. Sequencing platforms vary widely and may refer to targeted and small panels of < 100 genes, large panels of > 100 genes, whole-exome sequencing (WES)/whole-genome sequencing (WGS), and RNASeq. Many commercial platforms have emerged for tumor or tumor-normal sequencing, including FoundationOne CDx, Caris CDx, TempusXT, and Oncomine Comprehensive Assay (11). Some institutions have also adapted these assays for in-house profiling efforts, whereas others have developed their own sequencing plat forms, such as the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) platform, which is a hybridization capture–based assay (12). WES and WGS are still less frequently performed but provide additional data that are not confined to genes cov ered on a single panel and are often used in a research-based setting. With the increasing prevalence of large panel testing in oncology, a question that is often en countered in practice is whether or not an alteration is germline (present in all or most tissue) or somatic (present in tumor cells but not in other tissues). Importantly, panels are not able to distin guish if a variant is germline or somatically acquired, if tumor-only testing was performed, rather than tumor paired with a matched normal sample (such as blood). Additionally, when germline variants are identified, there is a lack of consensus on which genes may warrant germline-focused analysis and, furthermore, what degree of penetrance is required to determine cancer risk. Groups such as the European Society of Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) have established guidelines for germline-focused analysis to allow oncologists to navigate

these challenging clinical questions (13). Unveiling the Transcriptome

Transcriptomics is broadly defined as the analysis of messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), micro RNA (miRNAs), and long non-coding RNAs (ncRNAs). High-throughput transcriptional sequencing by RNASeq gives precise details on base pair sequences and additional RNAs that cannot be identified with the conventional microarray technology (14). Following the isolation of RNA from a given tissue, it is then converted to complementary DNA (cDNA) by reverse

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