125P - Comparison of microarray and next-generation sequencing-based approaches for detection of homologous recombination deficiency

Background

Presence of homologous recombination repair deficiency (HRD) in cancer cells is a biomarker for predicting responses to anticancer treatments acting through synthetic lethality, such as PARP inhibitors. HRD detection relies on functional or genomic approaches measuring genomic scars or genomic instability resulting from lack of functioning repair mechanisms. We evaluated 2 whole-genome microarray data analysis approaches for detecting HRD in cancer samples, compared to next-generation sequencing (NGS).

Methods

In total 212 FFPE samples were tested with OncoScan™ CNV Plus Assay for Research. Data was analyzed using 2 different approaches based on previously published methods: MTD1 (based on whole genome doubling events) and MTD2 (based on copy number analysis) with Chromosome Analysis Suite Version 4.3.0.71, Rstudio Version 2023.09.1+494, and R version 4.3.2. For all samples the HRD score obtained using a commercially available NGS-based assay was available for comparison. The sample cohort was split into the training (N=124 samples) and validation cohort (N=88 samples). Positive (PPA), negative (NPA) and overall percent agreements (OPA) between the microarray and commercial NGS-based approach were calculated.

Results

Analysis of 124 samples using MTD1 detected 30 samples with HRD. When compared to the commercially available HRD test the OPA was 88.7% (95% CI, 81.9-93.1%), with PPA of 80.8% (95% CI, 62.1-91.5%) and NPA of 90.82% (95% CI, 83.5-95.1%). MTD2 analysis approach of the same sample set detected HRD in 24 samples, reaching an OPA of 91.9% (95% CI, 85.8-95.6%), with PPA of 76.9% (95% CI, 57.9-89.0%) and NPA of 95.92% (95% CI, 90.0-98.4%). The analysis of the second sample cohort of 88 samples with MTD2 detected 41 samples with HRD and yielded similar agreement to the commercially available HRD test with OPA of 84.4% (95% CI, 75.1-90.3%), PPA of 80.0% (95% CI, 66.18-89.1%) and NPA of 88.37% (95% CI, 75.5-94.9%).

Conclusions

The Applied Biosystems^TM OncoScan^TM CNV Plus Assay for Research offers a reliable and cost-effective alternative to NGS-based approaches for detection of HRD and can contribute to expanding access to HRD testing for cancer research.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Thermo Fisher Scientific.

Disclosure

C. Kidwell, A. Crawford: Financial Interests, Personal, Full or part-time Employment: Quantigen. M. Napier, A. Roter, D. Woo, J.S. Milosevic Feenstra: Financial Interests, Personal, Full or part-time Employment: Thermo Fisher Scientific.