Abstract
The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.
Highlights
Traditional methods for tumor characterization are tumor-type specific and include assays such as immunohistochemistry (IHC), in situ hybridization (ISH), quantitative polymerase chain reaction (PCR), Sanger sequencing and gene signature microarrays [1,2,3,4,5,6,7,8]
The Roche Cobas quantitative PCR (qPCR) platform has FDA approved in vitro diagnostic (IVD)
An next generation sequencing (NGS) cancer panel was approved by Palmetto for patients with advanced non-small cell lung cancer, patients must have previously tested negative for EGFR mutations, ALK rearrangements and ROS1 rearrangements through non-NGS methods (MolDX: NSCLC, Comprehensive Genome Profile Testing (L35896))
Summary
Traditional methods for tumor characterization are tumor-type specific and include assays such as immunohistochemistry (IHC), in situ hybridization (ISH), quantitative PCR (qPCR), Sanger sequencing and gene signature microarrays [1,2,3,4,5,6,7,8]. The assay needs to have a simplified wet lab work-flow as well as a variant reporting structure which makes it possible to deliver results to the clinician in a timely manner („14 days) Another important component of diagnostic testing is the costs associated and the potential for insurance reimbursement. Labs will need to navigate the regulatory pathway to FDA and Medicare approval This will take time to gather the appropriate data to illustrate the benefit in treatment outcomes based on comprehensive testing and off-label drug use. An NGS cancer panel was approved by Palmetto (a contractor for the Centers for Medicare and Medicaid Services) for patients with advanced non-small cell lung cancer, patients must have previously tested negative for EGFR mutations, ALK rearrangements and ROS1 rearrangements through non-NGS methods (MolDX: NSCLC, Comprehensive Genome Profile Testing (L35896)). There is little doubt over time NGS based cancer diagnostics will be a key component in guiding personalized drug selection and shift the paradigm in how clinicians treat patients
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