Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer.
Por:
Moreno-Cabrera JM, Del Valle J, Feliubadaló L, Pineda M, González S, Campos O, Cuesta R, Brunet J, Serra E, Capellà G, Gel B and Lázaro C
Publicada:
1 ene 2022
Ahead of Print:
20 nov 2020
Resumen:
INTRODUCTION: Germline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest. METHODS AND RESULTS: We evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort. CONCLUSION: Including an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.
Filiaciones:
Moreno-Cabrera JM:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Hereditary Cancer Group, Program for Predictive and Personalized Medicine of Cancer - Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona, Spain
Del Valle J:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Feliubadaló L:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Pineda M:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
González S:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Campos O:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Cuesta R:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Brunet J:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Hereditary Cancer Program, Catalan Institute of Oncology, IDIBGi, Girona, Spain
:
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Hereditary Cancer Group, Program for Predictive and Personalized Medicine of Cancer - Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, Badalona, Spain
Capellà G:
Hereditary Cancer Program, Joint Program on Hereditary Cancer, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL-ONCOBELL, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Lázaro C:
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
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