| Autor: |
Adam B, Weiner, Yang, Liu, Matthew, McFarlane, Pushpinder S, Bawa, Eric V, Li, Xin, Zhao, Ziwen, Li, Tanya, Hammoud, Munna, Hazime, R Jeffrey, Karnes, Elai, Davicioni, Zachery R, Reichert, Arul M, Chinnaiyan, Tamara L, Lotan, Daniel E, Spratt, Edward M, Schaeffer |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Prostate cancer and prostatic diseases. 25(4) |
| ISSN: |
1476-5608 |
| Popis: |
Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P).By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n = 8224; metastatic castration-resistant PCa [mCRPC], n = 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations.HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n = 10), all three men with HRD-P+ experienced prolonged (330 days) PSA progression-free survival.These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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