Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer. Issue 1 (20th November 2020)

• Record Type: Journal Article
• Authors: Moreno-Cabrera, José Marcos; del Valle, Jesús; Feliubadaló, Lidia; Pineda, Marta; González, Sara; Campos, Olga; Cuesta, Raquel; Brunet, Joan; Serra, Eduard; Capellà, Gabriel; Gel, Bernat; Lázaro, Conxi
• Is Part Of: Journal of medical genetics. Volume 59:Issue 1(2022)
• Page Start: 75
• Page End: 78
• Publication Date: 2020-11-20
• Subjects: genetic testing -- germ-line mutation -- molecular diagnostic techniques; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2020-107366
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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.