Which statement about sequencing strategies for MRD is correct?

• A. Exome sequencing identifies more variants than whole genome sequencing
• B. Whole genome sequencing and exome sequencing have identical sensitivity
• C. Whole genome sequencing identifies significantly more tumor variants than exome sequencing
• D. Targeted panel sequencing is broader than whole genome sequencing

Answer: (C)

Whole-genome sequencing surveys the entire genome, including noncoding regions, whereas exome sequencing targets only the coding portions. Because many tumor mutations lie outside exons—in introns, regulatory regions, and in structural variants—whole-genome sequencing reveals a larger pool of detectable tumor variants than exome sequencing. In the context of MRD, this broader scope means more variants can potentially be identified, though sensitivity for any single low-frequency event often depends on sequencing depth and error suppression, which targeted deep panels prioritize for ultra-high detection. So, when considering the total number of tumor variants detectable, whole-genome sequencing identifies significantly more than exome sequencing. Exome sequencing cannot outpace WGS in variant discovery, their sensitivity is not identical due to differences in breadth and depth, and targeted panels are narrower, not broader, than whole-genome sequencing.