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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.
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).
In plain words · The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
This result usually explains why a hormone treatment has stopped working rather than changing what is offered next. It does not mean treatment has run out: the usual next steps are a different kind of treatment altogether, such as chemotherapy, a radioligand or, where the genetics allow it, a PARP inhibitor.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
High-level amplification of the AR locus at Xq12 on tumour or plasma sequencing, reported with the disease state at which the sample was taken, since prevalence runs from about 1% before treatment to about half after castration resistance.
“We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy.”
Visakorpi et al., Nature Genetics 1995No approval uses this readout as a threshold. It is defined by Quigley et al., Cell 2018: genomic hallmarks and structural variation in metastatic prostate cancer, including the AR upstream enhancer.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.
It shows that the useful information in a castration-resistant plasma sample is in the repair genes and TP53 rather than in the androgen receptor finding that dominates the report, and it is the closest thing the field has to a head-to-head comparison of abiraterone against enzalutamide.
The first evidence that resistance to hormone therapy in prostate cancer is an adaptation of the target rather than an escape from it, which is why the field kept building better androgen receptor drugs instead of abandoning the pathway.
Shares Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired), Circulating tumour DNA (ctDNA), Comprehensive genomic profiling and the tags biomarker, resistance.
Shares Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired), Comprehensive genomic profiling, Liquid biopsy (ctDNA) and the tags biomarker, resistance.
Shares Circulating tumour DNA (ctDNA) and the tags biomarker, resistance.
Shares Prostate cancer (KEGG map), Androgen receptor signalling, Metastatic hormone-sensitive prostate cancer, Castration-resistant prostate cancer (CRPC) and the tag biomarker.
Shares the tags biomarker, resistance.
Shares the tags biomarker, resistance.
Shares AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L), Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC).
Shares Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA) and the tag biomarker.