SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population-Reference-Cited by-同舟云学术

SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population

Published:2024 Issue: Volume:2024 Page:
ISSN:1758-0463
Container-title:Database
language:en
Short-container-title:

Author:

Moreno-Cabrera José M¹²³^ORCID,Feliubadaló Lidia¹²^ORCID,Pineda Marta¹²,Prada-Dacasa Patricia¹²,Ramos-Muntada Mireia¹²,Del Valle Jesús¹²^ORCID,Brunet Joan¹²^ORCID,Gel Bernat⁴^ORCID,Currás-Freixes María⁵,Calsina Bruna⁵^ORCID,Salazar-Hidalgo Milton E⁵,Rodríguez-Balada Marta⁶,Roig Bàrbara⁶,Fernández-Castillejo Sara⁶,Durán Domínguez Mercedes⁷,Arranz Ledo Mónica⁷,Infante Sanz Mar⁷,Castillejo Adela⁸,Dámaso Estela⁸^ORCID,Soto José L⁸,de Miguel Montserrat⁹,Hidalgo Calero Beatriz⁹,Sánchez-Zapardiel José M⁹,Ramon Y Cajal Teresa¹⁰,Lasa Adriana¹¹¹²,Gisbert-Beamud Alexandra¹³,López-Novo Anael¹⁴,Ruiz-Ponte Clara¹²¹⁴,Potrony Miriam¹²¹⁵,Álvarez-Mora María I¹²¹⁵,Osorio Ana¹²¹⁶,Lorda-Sánchez Isabel¹²¹⁶,Robledo Mercedes¹²¹⁷^ORCID,Cascón Alberto¹²¹⁷,Ruiz Anna¹⁸,Spataro Nino¹⁸,Hernan Imma¹⁹,Borràs Emma¹⁹,Moles-Fernández Alejandro²⁰²¹,Earl Julie²²²,Cadiñanos Juan²³,Sánchez-Heras Ana B²⁴,Bigas Anna²²⁵²⁶,Capellá Gabriel¹²,Lázaro Conxi¹²

Affiliation:

1. Hereditary Cancer Program, Catalan Institute of Oncology, Institut d’Investigació Biomèdica de Bellvitge-IDIBELL-ONCOBELL , L’Hospitalet de Llobregat, Barcelona 08908, Spain

2. Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III , Monforte de Lemos, 3-5, Madrid, 28029, Spain

3. Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO) , L’Hospitalet del Llobregat, Barcelona 08908, Spain

4. Hereditary Cancer Group, Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti , Ctra de Can Ruti, Camí de les Escoles, s/n, Badalona 08916, Spain

5. Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO) , Melchor Fernández Almagro, 3, Madrid 28029, Spain

6. Institut d’Oncologia de la Catalunya Sud (IOCS), Hospital Universitari Sant Joan de Reus (HUSJR), Institut d’Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV) , Dr. Josep Laporte, 2, Reus 43204, Spain

7. Cancer Genetics Group, Unit of Excellence Institute of Biomedicine and Molecular Genetics, University of Valladolid-Spanish National Research Council (IBGM, UVa- CSIC) , Sanz y Fores, 3, Valladolid 47003, Spain

8. Unidad de Genética Molecular, Hospital General Universitario de Elche. Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) , Av. de Catalunya, 21, Elche 03203, Spain

9. Laboratorio de cáncer hereditario, Servicio de Bioquímica clínica-Análisis clínicos, Hospital Universitario 12 de Octubre , Av. de Córdoba, s/n, Madrid 28041, Spain

10. Familial Cancer Clinic, Medical Oncology, Hospital de la Santa Creu i Sant Pau , Sant Quintí, 89, Barcelona 08041, Spain

11. Genetics Department, Hospital de la Santa Creu i Sant Pau , Sant Quintí, 89, Barcelona 08041, Spain

12. Biomedical Network Research Centre On Rare Diseases (CIBERER), Instituto de Salud Carlos III , Monforte de Lemos, 3-5, Madrid 28029, Spain

13. Institut de Recerca Sant Pau (IR Sant Pau) , Sant Quintí, 77, Barcelona 08041, Spain

14. Fundación Pública Galega de Medicina Xenómica (SERGAS), Instituto de Investigación Sanitaria de Santiago, Grupo de Medicina Xenómica-USC , Av. Barcelona, s/n, Santiago de Compostela 15706, Spain

15. Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona and Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), University of Barcelona , Rosselló, 149, Barcelona 08036, Spain

16. Departamento de Genética y Genómica, Hospital Universitario Fundación Jiménez Diaz (IIS-FJD) , Av. de los Reyes Católicos, 2, Madrid 28040, Spain

17. Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Center (CNIO) , Melchor Fernández Almagro, 3, Madrid 28029, Spain

18. Genetics Laboratory, Center for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona , Plaça Torre de l’Aigua, s/n, Sabadell 08208, Spain

19. Molecular Genetics Unit, Consorci Sanitari de Terrassa , Ctra. Torrebonica, S/N, Terrassa 08227, Spain

20. Department of Clinical and Molecular Genetics, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Hospital Universitari , Pg. de la Vall d’Hebron, 119, Barcelona 08035, Spain

21. Medicine Genetics Group, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Hospital Universitari , Pg. de la Vall d’Hebron, 119, Barcelona 08035, Spain

22. Biomarkers and Personalized Approach to Cancer Group (BioPAC), Ramón y Cajal Health Research Institute (IRYCIS) , Ctra. Colmenar Viejo, Km. 9,100, Madrid 28034, Spain

23. Fundación Centro Médico de Asturias , José María Richard Grandío, s/n, Oviedo, Asturias 33193, Spain

24. Cancer Genetic Counseling Unit, Medical Oncology Department, Elche General University Hospital , Almazara, 11, Elche 03203, Spain

25. Program in Cancer Research, Institut Hospital del Mar d’Investigacions Mèdiques , Dr. Aiguader, 88, Barcelona 08003, Spain

26. Josep Carreras Leukemia Research Institute , Ctra de Can Ruti, Camí de les Escoles, s/n, Barcelona 08916, Spain

Abstract

Abstract Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management. Database URL: https://spadahc.ciberisciii.es/

Funder

Instituto de Salud Carlos III and Ministerio de Ciencia e Innovación, funded by FEDER funds - a way to build Europe -

Department of Research and Universities of the Generalitat de Catalunya and AGAUR

CIBER - Consorcio Centro de Investigación Biomédica en Red

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/database/article-pdf/doi/10.1093/database/baae055/58867432/baae055.pdf

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