A Compendium of AR Splice Variants in Metastatic Castration-Resistant Prostate Cancer
Khrystany T Isebia1, Martijn P Lolkema1, Guido Jenster1
1Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands.
Abstract:
Treatment-induced AR alterations, including AR alternative splice variants (AR-Vs), have been extensively linked to harboring roles in primary and acquired resistance to conventional and next-generation hormonal therapies in prostate cancer and therefore have gained momentum. Our aim was to uniformly determine recurrent AR-Vs in metastatic castration-resistant prostate cancer (mCRPC) using whole transcriptome sequencing in order to assess which AR-Vs might hold potential diagnostic or prognostic relevance in future research. This study reports that in addition to the promising AR-V7 as a biomarker, AR45 and AR-V3 were also seen as recurrent AR-Vs and that the presence of any AR-V could be associated with higher AR expression. With future research, these AR-Vs may therefore harbor similar or complementary roles to AR-V7 as predictive and prognostic biomarkers in mCRPC or as proxies for abundant AR expression.
Insights
Androgen receptor splice variants (AR-Vs) drive prostate cancer resistance. This study identified recurrent AR-Vs, including AR45 and AR-V3, in metastatic castration-resistant prostate cancer (mCRPC), suggesting their potential as biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) alterations, including AR splice variants (AR-Vs), are implicated in prostate cancer resistance to hormonal therapies.
- Understanding recurrent AR-Vs is crucial for developing new diagnostic and prognostic tools.
Purpose of the Study:
- To uniformly identify recurrent AR-Vs in metastatic castration-resistant prostate cancer (mCRPC) using whole transcriptome sequencing.
- To assess the potential diagnostic or prognostic relevance of identified AR-Vs.
Main Methods:
- Whole transcriptome sequencing was employed to analyze AR-Vs in mCRPC samples.
- Recurrent AR-Vs were systematically identified and characterized.
Main Results:
- The study identified AR-V7, AR45, and AR-V3 as recurrent AR-Vs in mCRPC.
- The presence of any AR-V was associated with higher AR expression.
Conclusions:
- AR45 and AR-V3, in addition to AR-V7, are recurrent AR-Vs in mCRPC.
- These AR-Vs may serve as predictive and prognostic biomarkers or indicators of high AR expression in mCRPC.
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