ArticleJCO precision oncology2026
Shallow Whole-Genome Sequencing to Assess Genomic Instability and Predict Treatment Response in Metastatic Castration-Resistant Prostate Cancer.
Article in JCO precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
purposePatients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination deficiency (HRD) benefit from poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) or platinum-based chemotherapy (PlCh). Pathogenic variants in homologous recombination repair genes are used as a proxy for the phenotype. Genomic Instability Score (GIS) is a metric for the effect of HRD. This study used shallow whole-genome sequencing (sWGS), a cost-effective alternative to full-depth WGS, to calculate GIS and evaluate its predictive value for PARPi or PlCh response. PATIENTS AND
methodsWe analyzed 288 tumor samples from 266 patients with mCRPC, consisting of 120 whole-genome samples from formalin-fixed paraffin-embedded material newly profiled at a sequencing depth of 2× and 168 from fresh frozen material downsampled in silico from 106× to 2×. The GIS was defined as the sum of large-scale transitions, telomeric-allelic imbalances, and genomic loss of heterozygosity.
resultsThe median GIS was 26 (IQR, 19-37). Samples with pathogenic variants in
conclusionGIS assessment by sWGS is feasible and associated with response to PARPis and PlCh. The combination of BRCA-complex status and GIS is superior to BRCA-complex status alone in predicting PSA response to PARPis but not to PlCh.
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