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

• A. It separates inherited germline variants from tumor-acquired somatic changes, informing familial risk counseling and targeted therapy decisions.
• B. It sequences only tumors and not normal tissue.
• C. It is used only to predict response to therapy.
• D. It replaces germline testing.

Answer: (A)

Determining whether BRCA alterations are inherited or tumor-specific is the key idea here. Tumor-normal sequencing uses matched normal tissue to see if a BRCA change found in the tumor is present in every cell (germline) or only in the tumor (somatic).

If a BRCA alteration is germline, it means there is inherited risk for the patient and potentially other family members. This drives genetic counseling, cascade testing for relatives, and risk-reducing or surveillance strategies. At the same time, knowing the tumor carries a BRCA defect supports targeted therapy decisions—BRCA-deficient tumors often respond to PARP inhibitors and can be more sensitive to platinum-based chemotherapy.

If the BRCA change is only in the tumor, there is no inherited risk to relatives based on that finding, and management for relatives would not be driven by BRCA in this patient. Importantly, tumor-normal sequencing does not replace germline testing; confirming inherited risk still requires analysis of normal DNA.