Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases

被引：68

作者：

Kallio, Heini M. L. ^{[1
,2
]}

Hieta, Reija ^{[1
,2
]}

Latonen, Leena ^{[1
,2
]}

Brofeldt, Anniina ^{[1
,2
]}

Annala, Matti ^{[1
,2
]}

Kivinummi, Kati ^{[1
,2
]}

Tammela, Teuvo L. ^{[3
]}

Nykter, Matti ^{[1
,2
]}

Isaacs, William B. ^{[4
]}

Lilja, Hans G. ^{[1
,2
,5
,6
,7
,8
,9
]}

Bova, G. Steven ^{[1
,2
]}

Visakorpi, Tapio ^{[1
,2
,10
]}

机构：

[1] Univ Tampere, Prostate Canc Res Ctr, Fac Med & Life Sci, Tampere, Finland

[2] Univ Tampere, BioMediTech Inst, Tampere, Finland

[3] Univ Tampere, Tampere Univ Hosp, Dept Urol, Tampere, Finland

[4] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA

[5] Mem Sloan Kettering Canc Ctr, Dept Surg Urol, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10021 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[8] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England

[9] Lund Univ, Dept Translat Med, Malmo, Sweden

[10] Tampere Univ Hosp, Fimlab Labs, Tampere, Finland

来源：

BRITISH JOURNAL OF CANCER | 2018年 / 119卷 / 03期

基金：

芬兰科学院;

关键词：

CELL-FREE DNA; GENE; PROGRESSION; ABIRATERONE; ENZALUTAMIDE; MUTATIONS; THERAPY; GROWTH; AMPLIFICATION; ANTIANDROGEN;

D O I：

10.1038/s41416-018-0172-0

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: A significant subset of prostate cancer (PC) patients with a castration-resistant form of the disease (CRPC) show primary resistance to androgen receptor (AR)-targeting drugs developed against CRPC. As one explanation could be the expression of constitutively active androgen receptor splice variants (AR-Vs), our current objectives were to study AR-Vs and other AR aberrations to better understand the emergence of CRPC. METHODS: We analysed specimens from different stages of prostate cancer by next-generation sequencing and immunohistochemistry. RESULTS: AR mutations and copy number variations were detected only in CRPC specimens. Genomic structural rearrangements of AR were observed in 5/30 metastatic CRPC patients, but they were not associated with expression of previously known AR-Vs. The predominant AR-Vs detected were AR-V3, AR-V7 and AR-V9, with the expression levels being significantly higher in CRPC cases compared to prostatectomy samples. Out of 25 CRPC metastases that expressed any AR variant, 17 cases harboured expression of all three of these AR-Vs. AR-V7 protein expression was highly heterogeneous and higher in CRPC compared to hormone-naive tumours. CONCLUSIONS: AR-V3, AR-V7 and AR-V9 are co-expressed in CRPC metastases highlighting the fact that inhibiting AR function via regions common to all AR-Vs is likely to provide additional benefit to patients with CRPC.

引用

页码：347 / 356

页数：10

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