Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. RESULTS: All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. CONCLUSION: This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.

authors

publication date

  • April 16, 2021

Research

keywords

  • Biomarkers, Tumor
  • Genetic Testing
  • Genomics
  • Neoplasms
  • Oncogenes

Identity

PubMed Central ID

  • PMC8051090

Scopus Document Identifier

  • 85104386329

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdz205

PubMed ID

  • 33863344

Additional Document Info

volume

  • 22

issue

  • 1