What is the purpose of tumor-normal sequencing in BRCA mutation management?

• A. It separates inherited germline variants from somatic tumor changes, informing familial risk counseling and targeted therapy decisions.
• B. It sequences only tumor tissue.
• C. It replaces germline testing.
• D. It has no implications for therapy decisions.

Answer: (A)

Distinguishing inherited germline BRCA variants from tumor-specific somatic changes through tumor-normal sequencing is essential. By sequencing both the tumor and a normal sample (often blood), we can tell whether a BRCA alteration is present in all cells or only in the tumor. If it’s germline, the mutation is inherited and has implications for family risk: relatives may also carry the mutation and should be offered testing and appropriate surveillance or risk-reducing options. Therapy decisions also hinge on this distinction because germline BRCA status informs hereditary risk management and can influence treatment planning. If the mutation is somatic, it’s confined to the tumor and does not imply inherited risk, though it can still guide targeted therapy decisions, such as the potential use of PARP inhibitors in BRCA-deficient tumors. In short, this approach provides accurate classification that shapes both familial risk counseling and personalized treatment, while avoiding misinterpretation that could come from sequencing tumor tissue alone.