Functional characterization of BRCA2 variants of uncertain significance identified in Korean breast cancer patients.

Functional characterisation of three BRCA2 missense VUS (cisplatin/olaparib sensitivity, homologous recombination efficiency) in BRCA2-KO DLD-1 cells

Variants of uncertain significance (VUS) in BRCA2 remain a major challenge, especially in Asian populations where reference data are scarce. The authors select three BRCA2 missense VUS frequent in Korean cohorts and/or with strong family history, and characterise them functionally in BRCA2-KO DLD-1 cells. Cells expressing p.Asp1990Ala show increased sensitivity to cisplatin, ionising radiation and olaparib, comparable to pathogenic controls, with markedly reduced homologous recombination efficiency. The other variants behave differently.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A good demonstration of the value of functional assays for resolving BRCA2 VUS, with a reading directly relevant to PARP inhibitor eligibility. In under-represented populations, the key is to feed classification databases (ENIGMA/ClinVar) with robust functional evidence.

Analysis by Dr Thibaut Benquey