Which statement about MRD testing is least accurate?

• A. MRD monitoring uses ctDNA as a biomarker
• B. A positive MRD result indicates residual disease
• C. Whole genome sequencing is used to increase MRD sensitivity
• D. A negative MRD result means no tumor DNA is present in the blood ever

Answer: (D)

Minimal residual disease testing looks for tiny amounts of cancer DNA circulating in the blood, using ctDNA as a biomarker to detect residual disease after treatment and to help gauge relapse risk and guide further therapy. It relies on highly sensitive assays that can pick up very low allele frequencies of tumor DNA.

That makes the statement about using ctDNA as a biomarker true. It’s also true that a positive MRD result indicates residual disease is present, since detectable tumor DNA means cancer cells remain somewhere in the body.

The statement about using whole genome sequencing to increase MRD sensitivity is not accurate. MRD detection relies on extremely deep sequencing of specific tumor-derived mutations or targeted panels to achieve high sensitivity. Whole genome sequencing, while comprehensive, is not practical for MRD because it provides far less depth per locus at prohibitive cost, making it less sensitive for detecting very low levels of ctDNA.

The idea that a negative MRD result means no tumor DNA is present in the blood ever is too absolute. A negative result reflects no detectable DNA within the assay’s limit of detection at the time of testing; it does not guarantee the complete absence of tumor DNA in the blood at all times or in all body compartments, and ctDNA levels can rise with relapse or after later sampling.