Long-read sequencing bridges germline and somatic variant detection: a multi-modal approach for hereditary cancer diagnostics.

Multi-modal approach integrating liquid biopsy, short-read, and Nanopore long-read sequencing for simultaneous detection of germline and somatic variants

A multi-modal approach integrating liquid biopsy, short-read, and Nanopore long-read sequencing was prospectively evaluated in 50 hereditary cancer patients. Nanopore long-read enables detection of germline structural variants (SVs) and phasing, inaccessible with conventional short-read sequencing. 10% of actionable germline variants were identified only with the long-read approach, including structural deletions in predisposition genes. The combined modalities enable simultaneous characterization of germline and somatic variants in a single workflow.

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The germline-somatic bridge concept in long-read sequencing is clinically relevant in hereditary cancer, where management depends on both compartments. The 50-patient cohort is small for definitive conclusions, but demonstrates the feasibility of the multi-modal workflow in real clinical settings.

Clinical impact: 3/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 0/1 · Publication status: 0/1 → Total: 7/10