Variant | Gene | Type | COSMIC ID | DNA Change (Coding Nucleotide) | Exon |
---|---|---|---|---|---|
AR copy number gain | AR | CNV | |||
AR T878A | AR | missense | COSM236693 | 2632A>G | 8 |
AR H875Y | AR | missense | COSM238555 | 2623C>T | 8 |
AR copy number loss | AR | CNV | |||
AR any mutation | AR | any |
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.
Mutations in the Androgen Receptor are rare in untreated prostate cancer and have been described in 15-33% of castration resistant prostate cancer and hormone refractory tumors. Among these, the H875Y and T878A are recurrent mutations that have been previously described. These mutations alter responses to androgen receptor antagonists. Cases with two such mutations have been previously reported and the mutations may co-exist on the same allele.
This gene is a known cancer gene.
This gene is a known cancer gene.