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.

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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