Journal: European journal of human genetics : EJHG
This publication reviews how hereditary cancer testing has progressed from single‑gene assays to multigene panel testing, and now toward broader exome, genome, and long‑read sequencing approaches.
Key points:
- Multigene panel testing is currently the clinical standard for hereditary cancer evaluation, efficiently covering known predisposition genes in a single assay.
- Exome and genome sequencing are becoming increasingly practical for hereditary indications as sequencing costs decline and throughput improves. These approaches:
- Interrogate all coding exons (exome) or the entire genome (genome).
- Allow reanalysis over time as new cancer susceptibility genes are discovered.
- Support research into novel germline‑cancer associations.
- Long‑read sequencing is highlighted as an emerging technology with advantages over short‑read methods for:
- Detecting complex and structural variants.
- Resolving variants in difficult or paralogous regions (e.g., PMS2).
- Potentially improving diagnostic accuracy, reducing turnaround time, and identifying previously undetectable risk variants.
- Complementary testing approaches are emphasized, including germline DNA testing with RNA analysis and tumor sequencing to:
- Clarify variant impact (e.g., on splicing or expression).
- Improve interpretation of germline findings and overall diagnostic yield.
Overall, the authors provide a structured overview of current and emerging sequencing strategies for hereditary cancer testing, outlining their strengths, limitations, and practical opportunities for integration into routine clinical genetics.