A transcriptomic model for homologous recombination deficiency in prostate cancer.
Prostate Cancer Prostatic Dis
; 25(4): 659-665, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-34226663
ABSTRACT
BACKGROUND:
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).METHODS:
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.RESULTS:
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.CONCLUSION:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcriptoma
/
Neoplasias de Próstata Resistentes à Castração
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article