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.
- genetic testing
- germ-line mutation
- molecular diagnostic techniques
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Contributors JMM-C, JdV, LF, MP, SG, CLG performed the CNV analysis. OC, RC performed genetic tests. JMM-C, BG, ES, GC, JB contributed to analysis and presentation of the results. JMM-C, JdV, BG and CLG wrote the manuscript. All authors reviewed and accepted the manuscript.
Funding Contract grant sponsor: supported by the Carlos III National Health Institute funded by FEDER funds—a way to build Europe—(PI19/00553; PI16/00563, PI15/00854 and CIBERONC); the Government of Catalonia (Pla estratègic de recerca i innovació en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496) the Spanish Association Against Cancer (AECC) and Fundació La Marató de TV3.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study protocol was approved by the Ethics Committee of IDIBELL (PR278/19). Informed written consent was obtained from all of them.
Provenance and peer review Not commissioned; externally peer reviewed.
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