Moreover, although sequencing of paired normal blood or tissue samples is standard practice for research-oriented WES applications, many targeted panel approaches do not include matched normal samples. One effort demonstrated the ability of two large gene panels (315 or 573 genes) to predict mutational load for immunotherapy response in pilot patient cohorts, and another effort demonstrated the ability of one large gene panel (341 genes) to predict DNA mismatch repair protein deficient tumors through mutational load, although a systematic characterization of different tumor profiling strategies for both mutation load and personal neoantigen identification should inform their relative utilities for stratifying patients in emerging cancer precision medicine frameworks. For example, unlike targeted therapies linked to specific genetic lesions (e.g., epidermal growth factor receptor mutations and inhibitors), immune targeting strategies, such as checkpoint blockade or personalized cancer vaccines, may require large-scale ascertainment of mutational and neoantigen loads and individual mutation-associated neoantigens for personalized cancer vaccine development. Understanding the differences in genomic results between different tumor profiling approaches will become increasingly important as the cancer genome is leveraged to stratify patients for new therapeutic strategies. However, the benefits and limitations of these different sequencing strategies remain incompletely understood.
On the other end of the spectrum, clinical whole-exome sequencing (WES n ~ 20,000 genes) of matched tumor and germline samples has been studied through prospective sequencing efforts. Alternatively, panels that emphasize rapid turnaround time by profiling smaller gene sets (n = 15–48 genes) have also emerged. Such assays often consist of targeted sequencing panels that query a subset of typically 200–500 genes implicated in cancer biology or clinical management. Multiple tumor profiling approaches that leverage these advances have entered the clinic.
#Ducar and shepard driver
The mapping of the human genome, together with the advent of massively parallel sequencing, has accelerated discovery of driver genetic alterations in cancer and the development of drugs to target or otherwise exploit these events.
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