Detection of androgen receptor (AR) splice variants across diverse prostatic and non-prostatic tumor types using the TruSight Oncology 500 (TSO500) assay.

Pitel BA, Dasari S, Pryzbylski AL, +17 more, Gupta S.

Journal ArticleAbstract only — full text under license

AI summary — for doctors, generated from the abstract only

In a large-scale genomic screen of over 5,500 tumors, androgen receptor splice variants linked to hormone therapy resistance were found most often in prostate cancer, breast cancer, and salivary duct carcinoma, with rare occurrences in other tumor types, suggesting this testing approach could have value beyond prostate cancer alone.

What was studied

A pan-cancer genomic study profiling 5573 solid tumors using a comprehensive DNA/RNA sequencing panel to identify androgen receptor splice variants (AR-Vs), biomarkers of resistance to hormone therapy, and characterizing their clinicopathologic and molecular associations across diverse tumor types.

Key findings

AR-Vs were identified in 46 of 5573 tumors (0.8%) overall, with enrichment in prostate cancer (24/132, 18.2%), breast cancer (17/208, 8.2%), and salivary duct carcinoma (2/38, 5.3%), and rare occurrences in a lacrimal gland carcinoma and a juvenile granulosa cell tumor.
The AR-V7 variant was present in all 46 tumors (100%), but was the only detected variant (without other AR-Vs) in just 2 of 46 (4.3%) cases, meaning most tumors harbored multiple distinct AR-V species simultaneously.
Among patients with accessible treatment records, AR-Vs were found post-treatment in 2 of 8 (25%) prostate cancer patients treated with AR-signaling inhibitors and in 5 of 6 (83.3%) breast cancer patients after hormonal therapy, consistent with a role in treatment resistance.

Clinical relevance

The findings suggest that while AR-V testing is most clinically established in prostate cancer, its enrichment in breast cancer and salivary duct carcinoma suggests potential relevance for identifying hormone-therapy-resistant disease in these tumor types as well, though the authors note additional data are needed before broader clinical application.

Who should care

Pathology

Limitations

Detailed treatment history was available for only a subset of patients (8 prostate cancer and 6 breast cancer cases with AR-Vs), limiting the ability to draw firm conclusions about the relationship between AR-V detection and therapy resistance across the full cohort.

Androgen receptor splice variants linked to hormone therapy resistance occur most often in prostate and breast cancer but also appear in salivary duct carcinoma and rare other tumor types, suggesting broader potential relevance for treatment-resistance testing.

This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.

Abstract

Background

Androgen Receptor splice variants (AR-Vs) are known biomarkers of resistance to hormone therapy in prostate (CaP) and breast cancer (BC). However, pancancer interrogations of AR-Vs are lacking.

Methods

The MayoComplete Solid Tumor Panel, with DNA and RNA subpanels targeting 515 and 55 genes, respectively, was used to profile 5573 solid tumors. Relevant clinicopathologic and molecular features were summarized for tumors with detectable AR-Vs.

Results

AR-Vs were identified in 46 of 5573 (0.8%) tumors from 28 males and 18 females with a mean age of 68 years (range, 11 to 98). AR-Vs were enriched in CaP (24/132, 18.2%), BC (17/208, 8.2%), and salivary duct carcinomas (2/38, 5.3%), with rare occurrences in a lacrimal gland carcinoma and juvenile granulosa cell tumor. While AR-V7 was observed in all 46 tumors (100%), AR-V7 in the absence of other AR-Vs was seen in only 2 (of 46, 4.3%) tumors. Associated AR alterations in CaP included AR amplification (n = 3) and AR ligand binding domain (LBD) mutations (n = 2), while associated ESR1 variants in BC included ESR1 LBD mutations (n = 2) and ESR1 rearrangements (n = 2). Of patients with accessible medical records, 2/8 (25%) CaP patients had AR-Vs post-therapy with AR signaling inhibitors. Similarly, 5/6 (83.3%) BC patients had AR-Vs post-hormonal therapy. Notably, all 14 patients had multiple AR-V species.

Conclusions

Our results demonstrate enrichment of AR-Vs in prostate, breast, and salivary duct carcinomas, with rare occurrences in a lacrimal gland carcinoma and juvenile granulosa cell tumor. Multiple AR-Vs were frequently seen in the same tumor. Detection of AR-Vs may be clinically significant in prostate cancer and additional data is needed for other tumor types.

DOI

10.1016/j.humpath.2026.106260

PMID

42727615

Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.

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