As reported in Science Translational Medicine, Pitroda and colleagues developed a recombination proficiency score that measures the efficiency of DNA repair pathways in the context of cancer therapy aimed at generating DNA damage. The score is based on expression levels of four genes involved in DNA repair pathway preference (Rif1, PARI, RAD51, and Ku80), with high expression of these genes yielding a low score.
It was shown that carcinoma cells with low recombination proficiency score exhibit suppression of homologous recombination and frequent DNA copy number alterations, characteristic of the error-prone repair processes that are found in homologous recombination-deficient backgrounds.
The scoring system was clinically validated in patients with breast or non–small cell lung carcinomas (NSCLCs); it was shown that low recombinant proficiency score was associated with increased mutagenesis, adverse clinical features, and lower survival rates, indicating that suppression of homologous recombination contributes to the genomic instability that drives malignant progression. The adverse prognosis associated with low score was improved in NSCLC patients receiving adjuvant platinum-based chemotherapy, indicating that the adverse prognosis is counteracted by suppression of homologous recombination and associated sensitivity to platinum-based treatment.
The investigators concluded, “[The recombination proficiency score] may help oncologists select which therapies will be effective for individual patients, thereby enabling more personalized care.” ■
Pitroda SP, et al: Sci Transl Med 6:229ra42, 2014.