Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study.
Por:
Garcia-Casado Z, Oaknin A, Mendiola M, Alkorta-Aranburu G, Antunez-Lopez JR, Moreno-Bueno G, Palacios J, Yubero A, Marquez R, Gallego A, Sanchez-Heras AB, Lopez-Guerrero JA, Perez-Segura C, Barretina-Ginesta P, Alarcon J, Gaba L, Marquez A, Matito J, Cueva J, Palacio I, Iglesias M, Arcusa A, Sanchez-Lorenzo L, Guerra-Alia E, Romero I and Vivancos A
Publicada:
4 nov 2022
Resumen:
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% (g BRCA 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.
Filiaciones:
Garcia-Casado Z:
Molecular Biology Department, Fundacion Instituto Valenciano de Oncologia, 46009 Valencia, Spain
Oaknin A:
Medical Oncology Department, Vall d'Hebron Instituto de Oncologia, 08035 Barcelona, Spain
Mendiola M:
Instituto de Investigacion Biomedica del Hospital La Paz (IdiPAZ), 28029 Madrid, Spain
Centro de Investigacion Biomedica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III, 28029 Madrid, Spain
Alkorta-Aranburu G:
CIMA LAB Diagnostics/Universidad de Navarra, 31008 Pamplona, Spain
Antunez-Lopez JR:
Molecular Biology Department, Hospital Clinico Universitario Santiago, 15706 Santiago, Spain
Moreno-Bueno G:
Centro de Investigacion Biomedica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III, 28029 Madrid, Spain
Fundacion MD Anderson, 28033 Madrid, Spain
Departamento de Bioquímica, Instituto de Investigaciones Biomedicas 'Alberto Sols. Conexion Cancer (UAM-CSIC), Universidad Autonoma de Madrid (UAM), IdiPAZ, 28029 Madrid, Spain
Palacios J:
Centro de Investigacion Biomedica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III, 28029 Madrid, Spain
Pathology Department, Hospital Universitario Ramon y Cajal, 28034 Madrid, Spain
Faculty of Medicine, Alcala University, 28801 Madrid, Spain
Instituto Ramon y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain
Yubero A:
Medical Oncology Department, Hospital Clinico Universitario Lozano Blesa, 50009 Zaragoza, Spain
Marquez R:
Fundacion MD Anderson, 28033 Madrid, Spain
Gallego A:
Medical Oncology Department, Hospital Universitario La Paz, 28029 Madrid, Spain
Sanchez-Heras AB:
Medical Oncology Department, Hospital General Universitario de Elche, 03203 Elche, Spain
:
Molecular Biology Department, Fundacion Instituto Valenciano de Oncologia, 46009 Valencia, Spain
Universidad Catolica de Valencia, 46001 Valencia, Spain
Unidad Mixta de Investigacion en Cancer IVO-CIPF, 46009 Valencia, Spain
Perez-Segura C:
Medical Oncology Department, Hospital de Sant Pau i Santa Tecla, 43003 Tarragona, Spain
Barretina-Ginesta P:
Medical Oncology Department, Institut Catala d'Oncologia Girona, 17007 Girona, Spain
Alarcon J:
Medical Oncology Department, Hospital Universitario Son Espases, 07120 Palma de Mallorca, Spain
Gaba L:
Medical Oncology Department, Hospital Clinic de Barcelona, 08036 Barcelona, Spain
Marquez A:
Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, 29010 Malaga, Spain
Matito J:
Cancer Genomics Lab, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain
Cueva J:
Medical Oncology Department, Hospital Clinico Universitario Santiago, 15706 Santiago, Spain
Palacio I:
Medical Oncology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
Iglesias M:
Medical Oncology Department, Hospital Universitario Son LLatzer, 07198 Palma de Mallorca, Spain
Arcusa A:
Medical Oncology Department, Hospital de Terrassa, 08227 Terrassa, Spain
Sanchez-Lorenzo L:
Medical Oncology Department, Clinica Universidad de Navarra, 31008 Pamplona, Spain
Guerra-Alia E:
Medical Oncology Department, Hospital Universitario Ramon y Cajal, 28034 Madrid, Spain
Romero I:
Medical Oncology Department, Instituto Valenciano de Oncologia, 46009 Valencia, Spain
Vivancos A:
Cancer Genomics Lab, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain
Green Published, Green Accepted, gold
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