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<p>We evaluated the clinical utility of target-enhanced whole-genome sequencing (TE-WGS) in comparison with targeted panel sequencing (TPS) for identifying clinically relevant genomic alterations in advanced prostate cancer. We applied TE-WGS to tumor/normal paired samples from patients with advanced prostate cancer previously tested with TPS during routine care. We compared the sensitivity of TE-WGS in detecting variants reported by TPS and assessed its added value in uncovering additional targetable alterations. A total of 45 samples from patients with advanced prostate cancer were analyzed using TE-WGS, which demonstrated 96.3% sensitivity in detecting clinically relevant variants reported by matched TPS. Furthermore, TE-WGS identified an additional 430 variants (85.0%) with clinical impact that were not reported by TPS. Notably, TE-WGS revealed rearrangements in DNA repair genes such as <i>BRCA1/2</i>, <i>RAD51B, NBN</i>, and <i>CDK12</i>. Overall, additional targetable alterations were detected by TE-WGS in 46.7% of samples, including 35.6% with no actionable findings by TPS, underscoring the added clinical value of WGS-based profiling. Our study highlights TE-WGS as a valuable complement to TPS, revealing clinically relevant targets that support its consideration in the management of advanced prostate cancer.</p>

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Comparison of whole genome sequencing with clinical targeted panel sequencing of metastatic prostate cancer: insights from real-world data

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月25日

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  • Majd Al Assaad,
  • Sangmoon Lee,
  • Alissa Semaan,
  • David C. Wilkes,
  • Jyothi Manohar,
  • Gloria Cheang,
  • Oudai Hassan,
  • Georgi Lukose,
  • Christina Fedorov,
  • Jesus Delgado-de la Mora,
  • Eda Nur Kozan,
  • Daniela Guevara,
  • Olivier Elemento,
  • Clara Hwang,
  • Scott Tagawa,
  • Ana M. Molina,
  • David M. Nanus,
  • Jones T. Nauseef,
  • Cora N. Sternberg,
  • Erin Connolly-Strong,
  • James P. Solomon,
  • Juan Miguel Mosquera

摘要

We evaluated the clinical utility of target-enhanced whole-genome sequencing (TE-WGS) in comparison with targeted panel sequencing (TPS) for identifying clinically relevant genomic alterations in advanced prostate cancer. We applied TE-WGS to tumor/normal paired samples from patients with advanced prostate cancer previously tested with TPS during routine care. We compared the sensitivity of TE-WGS in detecting variants reported by TPS and assessed its added value in uncovering additional targetable alterations. A total of 45 samples from patients with advanced prostate cancer were analyzed using TE-WGS, which demonstrated 96.3% sensitivity in detecting clinically relevant variants reported by matched TPS. Furthermore, TE-WGS identified an additional 430 variants (85.0%) with clinical impact that were not reported by TPS. Notably, TE-WGS revealed rearrangements in DNA repair genes such as BRCA1/2, RAD51B, NBN, and CDK12. Overall, additional targetable alterations were detected by TE-WGS in 46.7% of samples, including 35.6% with no actionable findings by TPS, underscoring the added clinical value of WGS-based profiling. Our study highlights TE-WGS as a valuable complement to TPS, revealing clinically relevant targets that support its consideration in the management of advanced prostate cancer.