# AR amplification (gene and upstream enhancer)

Source: https://onco.cc/biomarkers/ar-amplification/  
OnCo record `ar-amplification` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Extra copies of the gene for the androgen receptor. It is almost never present before hormone treatment and is found in about half of prostate cancers that have become resistant to it, which is why the stage the sample was taken at matters more than the result itself.

## Summary

High-level amplification of AR at Xq12 was the first molecular explanation of endocrine treatment failure in a solid tumour: it was present in 7 of 23 tumours recurring on androgen deprivation and in none of the pre-treatment specimens from the same men (Visakorpi 1995). Recomputed on cBioPortal, it is present in 217 of 444 samples (48.9%) in prad_su2c_2019, 78 of 150 (52.0%) in prad_su2c_2015 and 85 of 149 (57.0%) in prad_fhcrc, all castration-resistant, against 5 of 489 (1.0%) in the TCGA primary cohort and 17 of 424 (4.0%) in the metastatic castration-sensitive cohort prad_mcspc_mskcc_2020. A second amplification that no coding-exon panel can see accompanies it: an intergenic enhancer 624 kb upstream of AR is amplified in 81% of 101 deeply sequenced castration-resistant metastases and correlates with receptor expression (Quigley 2018). In plasma, AR amplification is the commonest finding in castration-resistant disease and adds nothing to standard prognostic markers on its own (Annala 2018); some potential AR resistance alteration, amplification included, was present in 940 of 2,213 evaluable plasma samples, 42% (Tukachinsky 2021).

## Fields

- Kind: Biomarker
- Last checked: 2026-09-25
- Also known as: AR amplification; androgen receptor amplification; AR gain; AR copy number gain; AR enhancer amplification; Xq12 amplification
- Tags: biomarker; resistance

## Sources

- Visakorpi et al., Nat Genet 1995: in vivo amplification of the androgen receptor gene in tumours recurring on androgen deprivation (23 recurrent tumours): https://doi.org/10.1038/ng0495-401
- Quigley et al., Cell 2018: genomic hallmarks and structural variation in 101 metastatic castration-resistant prostate cancers (deep whole genomes): https://doi.org/10.1016/j.cell.2018.06.039
- cBioPortal study prad_su2c_2019 (SU2C/PCF Dream Team, PNAS 2019; 444 metastatic castration-resistant samples from 429 patients, whole exome): https://www.cbioportal.org/study/summary?id=prad_su2c_2019

## Connected records

- biomarkers: [AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)](https://onco.cc/biomarkers/ar-ligand-binding-domain-mutation/), [AR-V7 splice variant](https://onco.cc/biomarkers/ar-v7-splice-variant/), [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Treatment-emergent neuroendocrine transformation (recognising it)](https://onco.cc/biomarkers/nepc-transformation/)
- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Prostate cancer (KEGG map)](https://onco.cc/pathways/prostate-cancer-signalling/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)
- terms: [Androgen deprivation therapy (ADT)](https://onco.cc/terms/adt/), [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Copy number alteration (CNA)](https://onco.cc/terms/copy-number-variation-term/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/)
- key papers: [Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer](https://onco.cc/key-papers/paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [Genomic hallmarks and structural variation in metastatic prostate cancer](https://onco.cc/key-papers/paper-quigley-structural-variation-mcrpc-cell-2018/), [In vivo amplification of the androgen receptor gene and progression of human prostate cancer](https://onco.cc/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/)

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