A 42-year-old woman with a BRCA2 germline mutation is treated with olaparib, which achieves synthetic lethality because her tumour cells already have impaired repair of double strand breaks by which pathway?

• A Base excision repair
• B Nucleotide excision repair
• C Mismatch repair
• D Homologous recombination ✓

Explanation

BRCA1 and BRCA2 are essential for error-free homologous recombination repair of DNA double strand breaks using the sister chromatid as template. Olaparib inhibits poly(ADP-ribose) polymerase (PARP), which handles single strand breaks; unrepaired single strand breaks collapse replication forks into double strand breaks, which the BRCA-deficient tumour cannot fix accurately. Base excision repair addresses deaminated or oxidised bases, nucleotide excision repair bulky lesions, and mismatch repair replication errors, none of which involve BRCA.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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