digitalMLPA Uncovers CNVs in Hereditary Cancer Cases Missed by NGS Alone
As NGS continues to transform hereditary cancer diagnostics, important gaps remain – particularly when it comes to the detection of CNVs. Uneven read depth and limitations in CNV‑calling algorithms of multigene NGS panels can leave clinically relevant structural variants undetected.
A recent study by researchers at the Hacettepe University, published in the Molecular Biology Reports journal, highlights how D001 Hereditary Cancer Panel 1, can bridge this gap and provide clinically relevant insights where standard NGS falls short. The study evaluated 48 patients with a clear clinical suspicion of hereditary cancer who had previously received negative results from multigene NGS panel testing.
Key findings:
- Clinically relevant CNVs were identified in 4 unrelated families, representing an additional 8.5% diagnostic yield in otherwise NGS‑negative cases.
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Detected CNVs involved MLH1 and CDKN2A, each showing strong clinical correlation through tumour immunohistochemistry, familial segregation, or personal medical history.
- All of these variants would have remained undetected using sequencing‑only pipelines, demonstrating the persistent blind spot for structural variants in NGS-only workflows.
The authors conclude that digitalMLPA is a practical method suitable for routine workflow integration which, when combined with rigorous confirmation of single-probe findings, offers a robust strategy to improve genetic counselling and risk management.
Explore our website for more information on D001 Hereditary Cancer Panel 1 or the extended D002 Hereditary Cancer Panel 2 or contact us at info@mrcholland.com.
Why use digitalMLPA? Key benefits include:
- Reliable CNV detection with reduced chance of incidental findings
- Integration into existing NGS workflows
- Minimal DNA input – only 20 ng required
- Fast turnaround – from DNA sample to sequencer in <24 hours
- User-friendly analysis with Coffalyser digitalMLPA – no bioinformatics expertise needed
- Cost-effective: priced at ~35-40 EUR*
* Costs based on digitalMLPA reagent list prices; possible additional costs not included. Prices may differ when ordering through our sales partners.