Why is whole genome sequencing important for MRD sensitivity?

• A. It identifies significantly more tumor variants than exome sequencing
• B. It is cheaper than exome sequencing
• C. It only sequences noncoding regions
• D. It provides faster results

Answer: (A)

MRD sensitivity relies on detecting tumor-derived DNA among normal DNA by tracking tumor-specific variants. Whole genome sequencing surveys the entire genome, capturing far more somatic variants than exome sequencing, including coding and noncoding mutations, copy-number changes, and structural rearrangements. With a larger set of tumor-specific markers, you can detect much smaller amounts of residual tumor DNA in blood or bone marrow, boosting sensitivity. Exome sequencing covers only coding regions, so it misses many noncoding and structural variants that could serve as MRD markers. The option claiming it sequences only noncoding regions is incorrect. Also, MRD sensitivity is not primarily about speed or cost—though WGS is more resource-intensive—its comprehensive variant discovery provides the most markers to detect minimal residual disease.