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Optimizing NGS Testing in Clinical Practice: Approach by Pathologist

NextEdge Admin

30 Apr 2024

2 min 39 sec

The pathologist plays a pivotal role in tailoring targeted NGS panels in collaboration with oncologists, defining genes and genomic alterations for interrogation based on available approved drugs and access to clinical trials. Clinical NGS assays must consider sample types, minimum input DNA/RNA, and turnaround times, with targeted NGS offering higher sequencing depth and sensitivity, especially for samples with low tumor cell content.

NGS is commonly performed on tumor material from formalin-fixed, paraffin-embedded (FFPE) tissues and cytological samples, with pathological evaluation essential for confirming diagnosis, assessing sample adequacy, and estimating tumor cell content. Morphology-guided dissection enriches tumor DNA/RNA, with pre-analytical processing compatible with NGS. Tissue-sparing histopathological analysis maintains sufficient tumor tissue for molecular diagnostics, crucial for interpreting NGS results accurately.

NGS workflows encompass DNA/RNA extraction, target enrichment, library preparation, massive parallel sequencing, bioinformatics analysis, and variant interpretation. Clinical NGS focuses on targeted gene panels, enriching selected regions of interest via amplicon or hybridization capture, detecting various genomic alterations including SNVs, indels, CNVs, gene fusions, and complex biomarkers like tumor mutational burden and mutational signatures.

Assay validation is critical, assessing accuracy, precision, limits of detection, sensitivity, and specificity using molecular standards, reference samples, or clinical specimens with known mutations. Adherence to international quality standards like ISO15189 and participation in external quality assurance programs maintain quality.

Pathologist should consider tumor sample quality and feasibility of NGS during tumor board discussions, with awareness of assay validation and laboratory participation in EQA programs ensuring high-quality molecular analyses. Collaboration between pathologists, oncologists, and molecular diagnostics laboratories is essential for effective utilization of NGS in guiding personalized treatment decisions for cancer patients.