A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients.

Autor:	Feliubadaló L; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Oncobell Program, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Moles-Fernández A; Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Santamariña-Pena M; Fundación Pública Galega Medicina Xenómica (FPGMX), SERGAS, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain., Sánchez AT; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Oncobell Program, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain., López-Novo A; Fundación Pública Galega Medicina Xenómica (FPGMX), SERGAS, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain., Porras LM; Research Unit in Clinical and Translational Bioinformatics, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain., Blanco A; Fundación Pública Galega Medicina Xenómica (FPGMX), SERGAS, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain., Capellá G; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Oncobell Program, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., de la Hoya M; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain., Molina IJ; Institute of Biopathology and Regenerative Medicine, Center for Biomedical Research, Health Sciences Technology Park, Universtity of Granada, Granada, Spain., Osorio A; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.; Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Pineda M; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Oncobell Program, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Rueda D; Hereditary Cancer Laboratory, Doce de Octubre University Hospital, i+12 Research Institute, Madrid, Spain., de la Cruz X; Research Unit in Clinical and Translational Bioinformatics, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., Diez O; Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Clinical and Molecular Genetics Area, University Hospital Vall d'Hebron, Barcelona, Spain., Ruiz-Ponte C; Fundación Pública Galega Medicina Xenómica (FPGMX), SERGAS, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain., Gutiérrez-Enríquez S; Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Vega A; Fundación Pública Galega Medicina Xenómica (FPGMX), SERGAS, Santiago de Compostela, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain., Lázaro C; Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Oncobell Program, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Clinical chemistry [Clin Chem] 2021 Mar 01; Vol. 67 (3), pp. 518-533.
DOI:	10.1093/clinchem/hvaa250
Abstrakt:	Background: Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. Methods: Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. Results: Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. Conclusions: Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management. (© American Association for Clinical Chemistry 2020.)
Databáze:	MEDLINE
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