Journal Article

Paired comparison of the analytical performance between the Oncomine™ Comprehensive Assay v3 and whole-exome sequencing of ovarian cancer tissue

Schejbel, Lone, Høgdall, Estrid V., Lopacinska-Jørgensen, Joanna, Poulsen, Tim Svenstrup, Vestergaard, Lau K., Høgdall, Claus K.

2024

Overview

Background Next-generation sequencing (NGS) has been implemented in clinical oncology as a personalized medicine tool to identify targetable genetic alterations and to guide treatment decisions. However, the optimal NGS test strategy and target genes for clinical use are still being discussed. The aim was to compare the performance of the Oncomine™ Comprehensive Assay v3 (OCAv3) (targeted gene panel) and whole-exome sequencing (WES) to investigate somatic single and multiple nucleotide variants and small indels in ovarian cancer patients. Methods and results Genomic DNA was isolated from fresh frozen samples of five high-grade serous (HGSC) and three clear cell ovarian (oCCC) cancer patients. Exome sequencing libraries were prepared by using the Ion AmpliSeq Exome RDY kit, whereas libraries for OCAv3 were prepared using by Ion AmpliSeq™ Library Kit Plus. Sequencing was performed using the Ion S5XL System (Thermo Fisher Scientific). When including only variants classified as pathogenic, likely pathogenic or unknown significance based on ClinVar database verdicts and comparing overlapping regions covered both by the OCAv3 assay and WES, 23 variants were detected by both assays. However, OCAv3 detected additionally two variants: ARID1A : p.Gln563Ter and TP53 : p.Ser261ValfsTer84 that have not passed WES filtering criteria due to low coverage. Conclusions With the present treatment possibilities, OCAv3 panel testing provided higher diagnostic yield due to better coverage. Our study emphasizes that WES, although offering the potential to identify novel findings in genes not covered by OCAv3, might overlook variants in genes relevant for OC.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Adult / Aged / Animal Anatomy / Animal Biochemistry / Biomedical and Life Sciences / Brief Report / DNA / DNA sequencing / DNA-Binding Proteins - genetics / Exome Sequencing - methods / Female / genes / High-Throughput Nucleotide Sequencing - methods / Histology / Humans / Life Sciences / Middle Aged / Morphology / Mutation - genetics / Next-generation sequencing / Ovarian cancer / ovarian neoplasms / Ovarian Neoplasms - diagnosis / Ovarian Neoplasms - genetics / p53 Protein / Patients / Precision medicine / Transcription Factors - genetics / Whole genome sequencing