Which statement correctly describes the impact of whole genome sequencing on MRD sensitivity?

• A. It reduces the number of detectable variants
• B. It provides identical results to exome sequencing
• C. It identifies significantly more tumor variants than exome sequencing
• D. It cannot detect circulating tumor DNA

Answer: (C)

Whole-genome sequencing expands the set of tumor variants used to track MRD, which boosts sensitivity. By surveying the entire genome, it captures not only coding mutations but also noncoding mutations, structural variants, and copy-number alterations that exome sequencing misses. Those additional variants provide more targets to monitor in circulating tumor DNA, so even if some subclones disappear or the tumor evolves, you have a richer signature to detect residual disease. In contrast, exome sequencing focuses on coding regions, leaving many potential MRD signals undiscovered. WGS can also detect ctDNA signals, including rearrangements and CNAs, that exome-based approaches might miss. Therefore, identifying significantly more tumor variants with whole-genome sequencing explains its higher MRD sensitivity.