Detection of Clinically Significant BRCA Large Genomic Rearrangements in FFPE Ovarian Cancer Samples: A Comparative...

Area of Science:

• Genomics
• Molecular Diagnostics

Background:

• Copy number variations (CNVs) are critical in BRCA1/2 (BRCA) testing.
• Next-generation sequencing (NGS) is established for detecting large genomic rearrangements (LGRs).
• CNV detection in formalin-fixed paraffin-embedded (FFPE) samples presents challenges for routine clinical practice.

Purpose of the Study:

• To evaluate the performance of an amplicon-based NGS panel for detecting BRCA CNVs in FFPE samples.
• To assess the clinical utility of NGS-based CNV analysis in FFPE samples for ovarian cancer patients.

Main Methods:

• Analyzed 40 FFPE ovarian cancer samples using the Diatech Myriapod NGS BRCA1/2 panel.
• Compared NGS results with two hybrid capture-based reference assays for CNV detection.
• Assessed the ability to detect BRCA CNVs in FFPE samples.

Main Results:

• The Diatech NGS pipeline demonstrated good concordance with reference methods for BRCA CNV detection.
• All CNVs were correctly identified in 16 out of 17 CNV-positive samples with adequate sequencing quality.
• One result was inconclusive due to low sequencing quality.

Conclusions:

• NGS-based CNV analysis is clinically useful in FFPE samples when supported by appropriate bioinformatics tools.
• Integrating visual inspection and automated calling enhances CNV detection reliability.
• Accurate CNV detection from tumor tissue may decrease the need for germline testing, shortening turnaround times, but blood testing is essential for determining origin.