RT Journal Article
T1 Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study
A1 Garcia-Casado, Zaida
A1 Oaknin, Ana
A1 Mendiola, Marta
A1 Alkorta-Aranburu, Gorka
A1 Antunez-Lopez, Jose Ramon
A1 Moreno-Bueno, Gema
A1 Palacios, Jose
A1 Yubero, Alfonso
A1 Marquez, Raul
A1 Gallego, Alejandro
A1 Sanchez-Heras, Ana Beatriz
A1 Lopez-Guerrero, Jose Antonio
A1 Perez-Segura, Cristina
A1 Barretina-Ginesta, Pilar
A1 Alarcon, Jesus
A1 Gaba, Lydia
A1 Marquez, Antonia
A1 Matito, Judit
A1 Cueva, Juan
A1 Palacio, Isabel
A1 Iglesias, Maria
A1 Arcusa, Angels
A1 Sanchez-Lorenzo, Luisa
A1 Guerra-Alia, Eva
A1 Romero, Ignacio
A1 Vivancos, Ana
K1 Ovarian cancer
K1 BRCA mutations
K1 NGS
K1 BRCA testing
K1 Ring Test Trial
AB Germline and tumor BRCA 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) BRCA 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 gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA 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 BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA 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 BRCA status was 84.2% (gBRCA 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 BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.
PB MDPI
YR 2022
FD 2022-11-04
LK http://hdl.handle.net/10668/21392
UL http://hdl.handle.net/10668/21392
LA en
NO Garcia-Casado Z, Oaknin A, Mendiola M, Alkorta-Aranburu G, Antunez-Lopez JR, Moreno-Bueno G, et al. Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study. J Pers Med. 2022 Nov 4;12(11):1842
DS RISalud
RD Apr 20, 2025