Which sequencing approach yields greater breadth of tumor variant detection, enhancing MRD sensitivity?

• A. Whole genome sequencing
• B. Targeted panel sequencing
• C. Sanger sequencing
• D. RNA sequencing

Answer: (A)

Broad surveillance across the genome increases MRD sensitivity. Whole-genome sequencing surveys the entire genome, catching coding and noncoding regions and identifying a wide range of tumor-derived changes—single-nucleotide variants, small indels, copy-number alterations, and structural rearrangements—in one test. This breadth matters because minimal residual disease can consist of diverse clones with different mutations, so having a genome-wide view raises the chance of detecting a tumor-specific signal and strengthens confidence in MRD detection. In contrast, a targeted gene panel looks at a fixed set of loci, which means deep coverage for those sites but missing anything outside the panel, limiting breadth. Sanger sequencing is accurate but low-throughput and can only assess a few sites, making it insufficient for broad MRD detection. RNA sequencing focuses on expressed changes and may miss nonexpressed DNA alterations, making it less reliable for capturing residual tumor DNA. Therefore, whole-genome sequencing offers the broadest detection of tumor variants and the greatest potential to enhance MRD sensitivity.