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Interpretation 234
Tier 1
AR
Variants
AR copy number gain
Primary Sites
Prostate
Tumor Types
Adenocarcinoma
Small Cell Carcinoma
Interpretation

The androgen receptor (AR) is a ligand-dependent nuclear transcription factor. The AR gene undergoes multiple alterations leading to increased activity in prostate cancer, including gene amplification, point mutations, and alteration in splicing leading to constitutively active variants. However, these alterations take place largely, if not exclusively, in metastatic, castration resistant prostate cancer (CRPC). It is believed that lesions in the AR gene itself do not play a role in the pathogenesis of prostate cancer, but instead emerge during treatment as a mechanism of resistance to therapies targeting the androgen axis. Even in advanced cancers that no longer respond to androgen deprivation therapy, accumulating evidence has shown that AR signaling remains active and plays a critical role in disease progression. Androgen receptor activity, as inferred by the induction of AR target genes, was significantly increased in SPOP and FOXA1 mutant tumors when compared to normal prostate or ERG-positive tumors.

Citations
  1. Barbieri CE, et al. The mutational landscape of prostate cancer. Eur Urol 2013;64(4):567-76
  2. Cancer Genome Atlas Research Network The Molecular Taxonomy of Primary Prostate Cancer. Cell 2015;163(4):1011-25
Last updated: 2017-01-20 03:28:39 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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