Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study

• Published in: Journal of personalized medicine Vol. 12; no. 11; p. 1842
• Main Authors: Garcia-Casado, Zaida, Oaknin, Ana, Mendiola, Marta, Alkorta-Aranburu, Gorka, Antunez-Lopez, Jose Ramon, Moreno-Bueno, Gema, Palacios, Jose, Yubero, Alfonso, Marquez, Raul, Gallego, Alejandro, Sanchez-Heras, Ana Beatriz, Lopez-Guerrero, Jose Antonio, Perez-Segura, Cristina, Barretina-Ginesta, Pilar, Alarcon, Jesus, Gaba, Lydia, Marquez, Antonia, Matito, Judit, Cueva, Juan, Palacio, Isabel, Iglesias, Maria, Arcusa, Angels, Sanchez-Lorenzo, Luisa, Guerra-Alia, Eva, Romero, Ignacio, Vivancos, Ana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.11.2022; MDPI
• Subjects: BRCA mutations; BRCA testing; Breast cancer; Decision making; DNA repair; Gene frequency; Genes; Genetics; Genomes; Laboratories; Mutation; Next-generation sequencing; NGS; Ovarian cancer; Paraffin; Patients; Precision medicine; Reproducibility; Ring Test Trial; Software; Testing laboratories; Tumors; Womens health; United States > US; NGS; BRCA mutations; ovarian cancer; BRCA testing; Ring Test Trial
• ISSN: 2075-4426; 2075-4426
• DOI: 10.3390/jpm12111842

Germline and tumor testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known status in order to determine the inter-laboratory reproducibility of tissue testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to status was 84.2% (g 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3-70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting variants.