Introduction/Background Next-generation sequencing (NGS) can facilitate precision medicine in malignancies. So far, most NGS cancer panels can cover only small portion of the human genome, making it difficult to determine homologous recombination deficiency (HRD) status. However, advanced data analysis techniques might overcome current limitations of NGS cancer panels. Thus, we aimed to develop and validate an NGS cancer panel-based HRD test in patients with epithelial ovarian cancer (EOC).

Methodology We used data of SNUH FIRST Cancer Panel versions 3 and 4 on archival formalin-fixed paraffin-embedded tumor tissues obtained from EOC patients. Briefly, these panels use NextSeq550Dx platform (Illumina, Carlsbad, CA) and proves information on all exons of 184 genes (version 3) and 336 genes (version 4), specific introns of 23 fusion genes, the TERT promoter region, eight microsatellite-instability markers, and 45 drug-target regions, covering total length of approximately 2.06 (version 3) and 2.43 (version 4) Mbp, respectively. HRD scores were estimated by a modified algorithm of existing HRD calculation approach using pre-designed SNP sites. The validation was conducted by comparing the results of developed NGS cancer panel-based HRD test to that of ‘AmoyDx HRD test’.

Results In total, 155 patients were included in the development phase. High-grade serous was the most common histologic type (90.3%) and 28 patients (18.1%) had pathogenic BRCA1/2 mutations. Inaccurate estimation of HRD scores due to the rarity of targeted sequencing was calibrated using gap interpolation approach based on 1,558 pre-designed SNP sites. Nineteen specimens were used to validate the performance of a new algorithm. Of them, 26.3% had pathogenic BRCA1/2 mutations. Using the cut-off value of 42 for a new algorithm, the accordance rate between the two tests was 78.9%.

Conclusion We successfully developed NGS cancer panel-based HRD test algorithms. The incorporation of the new algorithm on NGS cancer panels might be useful to identify HRD-positive EOC cases.

Disclosures I have no conflict of interest to declare