What is tumor-normal sequencing and how does it inform patient care?

• A. It is used to determine prognosis only.
• B. It distinguishes inherited (germline) variants from tumor-specific (somatic) alterations, guiding treatment and familial risk counseling.
• C. It replaces germline testing entirely.
• D. It only detects copy number variants.

Answer: (B)

Tumor-normal sequencing compares the tumor's DNA with the patient's normal DNA to separate inherited germline variants from tumor-specific somatic mutations. This distinction matters because somatic changes can be the actual drivers of cancer and serve as targets for treatment, while germline variants reveal inherited cancer risk and guide family counseling and screening for relatives. In practice, it helps identify actionable alterations in the tumor to inform targeted therapies or clinical trial eligibility, and it flags germline changes that may require genetic counseling and cascade testing for family members. It does not replace germline testing entirely, since germline risk assessment is a separate process, and it detects more than just copy number variants, including various types of sequence changes and structural alterations.