Reliability and reproducibility among different platforms for tumour BRCA testing in ovarian cancer: a study of the Italian NGS Network

J Clin Pathol. 2021 Oct;74(10):668-672. doi: 10.1136/jclinpath-2020-206800. Epub 2020 Oct 5.

Abstract

Introduction: BRCA tumour testing is a crucial tool for personalised therapy of patients with ovarian cancer. Since different next-generation sequencing (NGS) platforms and BRCA panels are available, the NGS Italian Network proposed to assess the robustness of different technologies.

Methods: Six centres, using four different technologies, provided raw data of 284 cases, including 75 cases with pathogenic/likely pathogenic variants, for a revision blindly performed by an external bioinformatic platform.

Results: The third-party revision assessed that all the 284 raw data reached good quality parameters. The variant calling analysis confirmed all the 75 pathogenic/likely pathogenic variants, including challenging variants, achieving a concordance rate of 100% regardless of the panel, instrument and bioinformatic pipeline adopted. No additional variants were identified in the reanalysis of a subset of 41 cases.

Conclusions: BRCA tumour testing performed with different technologies in different centres, may achieve the realibility and reproducibility required for clinical diagnostic procedures.

Keywords: molecular; molecular biology; ovarian neoplasms; pathology.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor / genetics*
  • Computational Biology
  • Female
  • Genetic Heterogeneity*
  • Genetic Testing*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Italy
  • Observer Variation
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Workflow

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor