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Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing
Open accessAbstract
Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered.
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“We and other groups have identified tumor alterations that reactivate AR signaling during treatment with an ARSI2,22–29.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [25]
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“These mechanisms of resistance include AR gene amplification22,23, AR enhancer amplification2,24,25, AR mutation26, AR genomic structural rearrangements27, AR splice variants28 and polymorphisms in androgen metabolism genes29.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [25]
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ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,724
Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 11,073
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,965
Self-citationRecurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer
Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X.-W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., et al. (2005) · Science · doi:10.1126/science.1117679 · Cited by 3,846
Integrative Clinical Genomics of Advanced Prostate Cancer
Robinson, D., Van Allen, E. M., Wu, Y.-M., Schultz, N., Lonigro, R. J., Mosquera, J.-M., Montgomery, B., Taplin, M.-E., Pritchard, C. C., Attard, G., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.001 · Cited by 3,645
Self-citationThe Molecular Taxonomy of Primary Prostate Cancer
Abeshouse, A. A., Ahn, J., Akbani, R., Ally, A., Amin, S. B., Andry, C., Annala, M., Aprikian, A. G., Armenia, J., Arora, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.10.025 · Cited by 3,126
Self-citationAR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer
Antonarakis, E. S., Lu, C., Wang, H., Luber, B., Nakazawa, M., Roeser, J. C., Chen, Y., Mohammad, T. A., Chen, Y., Fedor, H. L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1315815 · Cited by 2,710
The mutational landscape of lethal castration-resistant prostate cancer
Grasso, C. S., Wu, Y.-M., Robinson, D. R., Cao, X., Dhanasekaran, S. M., Khan, A. P., Quist, M. J., Jing, X., Lonigro, R. J., Brenner, J. C., et al. (2012) · Nature · doi:10.1038/nature11125 · Cited by 2,517
Molecular determinants of resistance to antiandrogen therapy
Chen, C. D., Welsbie, D. S., Tran, C., Baek, S. H., Chen, R., Vessella, R., Rosenfeld, M. G., & Sawyers, C. L. (2004) · Nature Medicine · doi:10.1038/nm972 · Cited by 2,278
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., Nava Rodrigues, D., Robinson, D., Omlin, A., Tunariu, N., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1506859 · Cited by 2,185
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Items 201–300 of 374
Nyquist, M. D., Coleman, I. M., Lucas, J. M., Li, D., Hanratty, B. P., Meade, H. E., Mostaghel, E. A., Plymate, S. R., Corey, E., Haffner, M. C., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-2613 · Cited by 12
Self-citationCrumbaker, M., Chan, E. K. F., Gong, T., Corcoran, N. M., Jaratlerdsiri, W., Lyons, R. J., Haynes, A., Kulidjian, A., Kalsbeek, A. M. F., Petersen, D. C., et al. (2020) · Cancers · doi:10.3390/cancers12051178 · Cited by 12
“In general, genomic changes are thought to accumulate in response to treatment as the disease progresses and the importance of structural variants (SVs) in advanced prostate cancer is an evolving area of research [10,11].”
BackgroundXiang, R. R., Lee, S.-A., Tyndall, C. F., Bhatia, A. R., Yin, J., Singler, C., Hauk, B. J., Kipp, M. P., & Takeda, D. Y. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115312 · Cited by 11
“…the prominent role of the distal enhancer is supported by genomic data showing recurrent focal amplifications of the distal AR enhancer 10,11,34 and functional data demonstrating that the suppression of the distal AR enhancer decreases viability, while amplification is sufficient to…”
Germline and Somatic Defects in DNA Repair Pathways in Prostate Cancer
Arce‐Gallego, S., Athie, A., Pritchard, C. C., & Mateo, J. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-32656-2_12 · Cited by 11
Maranto, C., Sabharwal, L., Udhane, V., Pitzen, S. P., McCluskey, B. M., Qi, S., O’Connor, C., Devi, S., Johnson, S. C., Jacobsohn, K. M., et al. (2024) · Science Advances · doi:10.1126/sciadv.adi2742 · Cited by 11
Self-citationHaplotype-resolved germline and somatic alterations in renal medullary carcinomas
Tan, K. T., Kim, H., Carrot‐Zhang, J., Zhang, Y., Kim, W. J., Kugener, G., Wala, J. A., Howard, T. P., Chi, Y.-Y., Beroukhim, R., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00929-4 · Cited by 12
Self-citationLi, H., Melnyk, J. E., Fu, B. X. H., Shrestha, R., Zhang, M., Sjöström, M., Feng, S., Anderson, J. A., Han, W., Chesner, L. N., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02388-8 · Cited by 10
“These mechanisms of resistance include AR gene amplification 22,23 , AR enhancer amplification 2,24,25 , AR mutation 26 , AR genomic structural rearrangements 27 , AR splice variants 28 and polymorphisms in androgen metabolism genes 29 .”
Self-citationThe future of androgen receptor targeting in prostate cancer: third-generation inhibitors and beyond
Bernard‐Tessier, A., Naoun, N., Barraud, S., Flippot, R., Pobel, C., Rey, M., Baldini, C., Massard, C., Patrikidou, A., Fuerea, A. C., et al. (2025) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359251379416 · Cited by 10
“24 Additionally, structural truncating rearrangements can occur either concurrently or as a solitary alteration, leading to the production of constitutively active AR variants.”
Huttunen, J., Aaltonen, N., Helminen, L., Rilla, K. J., & Paakinaho, V. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05209-z · Cited by 10
“Furthermore, this enhancer is frequently amplified in CRPC patients, often coinciding with AR -gene amplification [53].”
BackgroundFanelli, G. N., Nuzzo, P. V., Pederzoli, F., & Loda, M. F. (2024) · Surgical pathology clinics · doi:10.1016/j.path.2024.10.003 · Cited by 12
Sun, R., Peng, J. C., Wang, Z., Yan, B., Zhu, S., Huang, Z., Zhang, J., Ding, D., Li, X., Wang, L., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2413732122 · Cited by 11
New frontiers in prostate cancer treatment from systemic therapy to targeted therapy
Nouruzi, S., Kobelev, M., Tabrizian, N., Gleave, M. E., & Zoubeidi, A. (2025) · EMBO Molecular Medicine · doi:10.1038/s44321-025-00282-8 · Cited by 13
“…(Fujita and Nonomura, 2019; Gottlieb et al, 2012; Linja et al, 2001; Robinson et al, 2015a), tandem duplication of AR enhancers (Quigley et al, 2018; Viswanathan et al, 2018), splice variants like AR-V7 (Cao et al, 2014) that allow AR to remain active without a ligand-binding domain (Guo et al,…”
Li, F., Luo, Q., Guo, T., Zhou, S., Cheng, Z., Pan, H., & Tu, J. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2561789 · Cited by 12
“This remarkable plasticity allows microglia to precisely balance neuroprotective and neuro-toxic effects in the CNS [58,59].”
AKR1C3 mediates pan‐AR antagonist resistance in castration‐resistant prostate cancer
Hertzog, J., Zhang, Z., Bignan, G., Connolly, P. J., Heindl, J. E., Janetopoulos, C., Rupnow, B. A., & McDevitt, T. M. (2020) · The Prostate · doi:10.1002/pros.24049 · Cited by 10
“The most common mechanism of resistance involves androgen receptor (AR) restoration, which results in the reactivation of the AR signaling pathway.(4,5) AR restoration frequently occurs as a result of genomic alterations in the AR gene and can include; AR amplification, AR activating mutations, and AR structural rearr…”
BackgroundSelf-citationLin, X., Wang, Z., Wu, X., Zeng, T., Luo, W., Hu, X., Ni, Y., Che, G., Liu, L., Zhang, W., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109660 · Cited by 10
Fusion oncogenes—genetic musical chairs
Imielinski, M. B., & Ladanyi, M. (2018) · Science · doi:10.1126/science.aau8231 · Cited by 10
Nucleolin represses transcription of the androgen receptor gene through a G-quadruplex
Miranti, C. K., Moore, S., Kim, Y., Chappeta, V. R., Wu, K., De, B., Gokhale, V. M., Hurley, L. H., & Reyes‐Reyes, E. M. (2020) · Oncotarget · doi:10.18632/oncotarget.27589 · Cited by 11
Analysis of CDK12 alterations in a pan‐cancer database
Pan, E., Cabal, A., Javier-DesLoges, J. F., Patel, D. N., Panian, J. A., Lee, S., Shaya, J. A., Nonato, T. K., Xu, X., Stewart, T. F., et al. (2021) · Cancer Medicine · doi:10.1002/cam4.4483 · Cited by 10
Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer
Eickhoff, N., Bergman, A. M., & Zwart, W. T. (2022) · Endocrinology · doi:10.1210/endocr/bqac153 · Cited by 10
Ware, K. E., Gupta, S. K., Eng, J., Kemeny, G., Puviindran, B. J., Foo, W., Crawford, L. A., Almquist, R. G., Runyambo, D., Thomas, B. C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.22.050385 · Cited by 10
“Additionally, alternative mechanisms can promote the AR transcriptome or promote AR activity through substitute methods of AR activation (Arora et al., 2013; Ware et al., 2014) to generate a pro-survival response (Chen et al., 2004; Viswanathan et al., 2018).”
BackgroundEpitranscriptomic mechanisms of androgen signalling and prostate cancer
Patke, R., Harris, A. E., Woodcock, C. L., Thompson, R., Santos, R. M., Kumari, A. A., Allegrucci, C., Archer, N., Gudas, L. J., Robinson, B. D., et al. (2024) · Neoplasia · doi:10.1016/j.neo.2024.101032 · Cited by 10
Smits, M., Ekici, K., Naga, S. P., van Oort, I. M., Sedelaar, J. P. M., Schalken, J. A., Nagarajah, J., Scheenen, T. W. J., Gerritsen, W. R., Fütterer, J. J., et al. (2020) · Cancers · doi:10.3390/cancers12123756 · Cited by 9
Fan, Y., Fan, H., Quan, Z., & Wu, X. (2021) · Cancer Investigation · doi:10.1080/07357907.2021.1899200 · Cited by 9
“Whole genome sequencing (WGS) studies have demonstrated that genomic structural variants, including genomic deletions, insertions, tandem duplications, inversion rearrangements, and interchromosomal recombination are more prevalent in mCRPC compared with localized prostate cancer (6,7).”
BackgroundALAN is a computational approach that interprets genomic findings in the context of tumor ecosystems
Bergom, H. E., Shabaneh, A., Day, A., Ali, A. A.-M., Boytim, E., Tape, S., Lozada, J. R., Shi, X., Kerkvliet, C. J. P., McSweeney, S. T., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04795-1 · Cited by 9
“AR mutations, ampli fi cation, or overexpression remain prevalent in patients that develop resistance to multiple therapies, which reinforce that AR functions remain critical in advanced cancers 6,10,24 – 27 .”
BackgroundSelf-citationMaestas-Olguin, A., Olewine, M., Thabata, S., Ebode, J. T., Arcos, M., Krawchuck, J. A., Coker, E. N., BREARLEY, A. J., Xue, X., Watt, J. D., et al. (2023) · Chemistry of Materials · doi:10.1021/acs.chemmater.3c01174 · Cited by 7
Lu, B., Liu, Y., Yao, Y., Yang, T., Zhang, H., Yang, X., Huang, R., Wang, Z., Pan, X., & Cui, X. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1355551 · Cited by 8
Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators
Feng, Y., Zhang, Y., Li, H., Wang, T., Lu, F., Liu, R., Xie, G., Song, L., Huang, B., Li, X., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06937-7 · Cited by 8
“In patients with CRPC, resistance to enzalutamide involves several aspects, including AR gene duplication [10, 11], AR splice variants (AR-Vs) [12], AR gene mutations [13] and upregulation of aberrant glucocorticoid receptor (GR) [14].”
A Splice Site Variant of CDK12 and Breast Cancer in Three Eurasian Populations
Bogdanova, N. V., Schürmann, P., Valova, Y. V., Dubrowinskaja, N., Turmanov, N., Yugay, T., Essimsiitova, Z., Mingazheva, E., Prokofyeva, D. S., Bermisheva, M., et al. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00493 · Cited by 8
van Dessel, L. F., Martens, J. W. M., & Lolkema, M. P. (2020) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000655 · Cited by 8
Sethi, R., Becker, J., de Graaf, J., Löwer, M., Suchan, M., Şahin, U., & Weber, D. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008397 · Cited by 9
Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review)
Lin, Y., & Jin, X. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.12321 · Cited by 10
“Tandem duplication has also been described as an AR enhancer, possibly associated with disease progression in androgen pathway inhibitors (40).”
BackgroundPham, M., Gupta, A., Gupta, H., Vaghasia, A. M., Skaist, A., Garrison, M. A., Coulter, J. B., Haffner, M. C., Zheng, S. L., Xu, J., et al. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-21-0683 · Cited by 8
“Long-read sequencing and linked-read sequencing have allowed comprehensive assessment of haplotypes and even end-to-end assem-blyofhuman genomes(8,11,12).”
Uusi-Mäkelä, J., Afyounian, E., Tabaro, F., Häkkinen, T., Lussana, A., Shcherban, A., Annala, M., Nurminen, R., Kivinummi, K. K., Tammela, T. L. J., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.08.287268 · Cited by 11
“Identified peaks include an enhancer known to be amplified in advanced PC ((Takeda et al., 2018; Viswanathan et al., 2018)).”
BackgroundGriffin: Framework for clinical cancer subtyping from nucleosome profiling of cell-free DNAPreprint
Doebley, A.-L., Ko, M., Liao, H., Cruikshank, A. E., Kikawa, C., Santos, K., Hiatt, J. B., Patton, R. D., Sarkar, N. D., Hoge, A. C. H., et al. (2021) · medRxiv · doi:10.1101/2021.08.31.21262867 · Cited by 8
Self-citationRoles of CDK12 mutations in PCa development and treatment
Jiang, C., Hong, Z., Liu, S., Hong, Z., & Dai, B. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189247 · Cited by 8
Stücheli, S., Araya, S., Ercan, C., Moser, S. O., Gallon, J., Jenö, P., Piscuoglio, S., Terracciano, L., & Odermatt, A. (2022) · Cancers · doi:10.3390/cancers14133074 · Cited by 6
Weiss, S., Lamy, P., Rusan, M., Nørgaard, M., Ulhøi, B. P., Knudsen, M., Kassentoft, C. G., Farajzadeh, L., Jensen, J. B., Pedersen, J. S., et al. (2024) · International Journal of Cancer · doi:10.1002/ijc.34949 · Cited by 9
Sequence of events in prostate cancer
Cotter, K. A., & Rubin, M. A. (2018) · Nature · doi:10.1038/d41586-018-06029-5 · Cited by 7
Wu, Y., Gui, Y., Wu, D., & Wu, Q. (2020) · Current Bioinformatics · doi:10.2174/1574893615999200901105208 · Cited by 7
Branch, J. R., Bush, T. L., Pande, V., Connolly, P. J., Zhang, Z., Hickson, I., Ondrus, J., Jaensch, S., Bischoff, J. R., Habineza, G., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0510 · Cited by 7
“These include mutations specific to the AR signaling pathway (AR aberrations): gene (5, 6) or enhancer (7) amplification, genomic structural rearrangement (8), splice variant isoform expression (9), ligand binding domain (LBD) point mutations (10, 11), adrenal and intraprostatic androgen synthesis (12–14), and glucoco…”
BackgroundSelf-citationZhang, Z., Connolly, P. J., Escolar, L. T., Rocaboy, C., Pande, V., Meerpoel, L., Lim, H., Branch, J. R., Ondrus, J., Hickson, I., et al. (2021) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00032 · Cited by 7
Self-citationPredicted Immunogenicity of CDK12 Biallelic Loss-of-Function Tumors Varies across Cancer Types
Elliott, A., Zhang, J., Zhang, Q. H., Swensen, J. J., Martin, D., Xiu, J., Geynisman, D. M., Vaena, D. A., Herzog, T. J., Holloway, R. W., et al. (2021) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.08.010 · Cited by 8
Stover, E. H., Oh, C., Keskula, P., Choudhury, A. D., Tseng, Y., Adalsteinsson, V. A., Lohr, J. G., Thorner, A. R., Ducar, M. D., Kryukov, G. V., et al. (2022) · The Prostate · doi:10.1002/pros.24305 · Cited by 7
“Prostate cancer‐specific targeted NGS panels can also identify targetable alterations with therapeutic implications in primary and metastatic prostate cancer, including BRCA2 mutations or deletions that may predict sensitivity to PARP inhibitors; CDK12 alterations and mismatch repair deficiency that may suggest sensit…”
BackgroundSelf-citationLercher, L., Simon, N., Bergmann, A., Tauchert, M. J., Bochmann, D., Bashir, T., Neuefeind, T., Riley, D., Danna, B., Krawczuk, P. J., et al. (2022) · SLAS DISCOVERY · doi:10.1016/j.slasd.2022.04.003 · Cited by 7
Nishimura, K., Mori, J., Sawada, T., Nomura, S., Kouzmenko, A., Yamashita, K., Kanemoto, Y., Kurokawa, T., Hayakawa, A., Tokiwa, S., et al. (2021) · Research and Reports in Urology · doi:10.2147/rru.s328661 · Cited by 6
“It has been suggested that increased AR protein expression after somatic enhancer acquisition and/or amplification of the AR cistron may confer androgen-independency at advanced prostate cancer stages.(13,14) These findings clearly indicate that AR signaling abnormalities during prostate cancer development can be attr…”
BackgroundKneppers, J., Bergman, A. M., & Zwart, W. T. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-11836-4_15 · Cited by 6
Future therapeutic strategies for metastatic prostate cancer
Smits, M., Gerritsen, W. R., & Mehra, N. (2019) · Tijdschrift voor Urologie · doi:10.1007/s13629-019-00261-y · Cited by 6
Eteleeb, A. M., Quigley, D. A., Zhao, S. G., Pham, D., Yang, R., Dehm, S. M., Luo, J. R., Feng, F. Y.-C., Dang, H. X., & Maher, C. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-71168-7 · Cited by 6
Self-citationTumor size and genomic risk in localized prostate cancer
Gaffney, C., Liu, D., Cooley, V., Ma, X., Angulo, C., Robinson, B. D., Khani, F., Cai, P. Y., Salami, S. S., Nallandhighal, S., et al. (2021) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2021.01.020 · Cited by 6
Martinez‐Fundichely, A., Dixon, A., & Khurana, E. (2022) · Nature Communications · doi:10.1038/s41467-022-32945-2 · Cited by 5
“The cancer types include those with a high SV burden from the PCAWG project 1,18 and metastatic prostate cancer samples 19,20 .”
BackgroundStitz, R., Stoiber, F., Silye, R., Vlachos, G., Andaloro, S., Rebhan, E.-M., Dunzinger, M., Pühringer, F., Gallo, C., Heliebi, A. E., et al. (2024) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2024.02.009 · Cited by 6
“40 More recently, recurrent complex rearrangements of the AR locus and structural alterations in the AR gene enhancers also were observed in many patients with CRPC. 41,42 A further limitation of this validation is the lack of certi fi ed reference material and external quality assessment.”
Vasiliou, S. K., Filippou, P. S., Clotet‐Freixas, S., Soosaipillai, A. R., Batruch, I., Tsianos, F. V., Konvalinka, A., & Diamandis, E. P. (2022) · Clinical Proteomics · doi:10.1186/s12014-022-09352-2 · Cited by 6
Peinetti, N., Bilušić, M., & Burnstein, K. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci165357 · Cited by 6
Systems-level liquid biopsy in advanced prostate cancer
Lyman, J. A., & Dehm, S. M. (2025) · Endocrine Related Cancer · doi:10.1530/erc-24-0274 · Cited by 5
Self-citationZhang, C., Mendez‐Dorantes, C., Burns, K. H., & Pellman, D. S. (2026) · Nature Genetics · doi:10.1038/s41588-025-02434-5 · Cited by 8
“6a. Adjacent parallel breakpoints in prostate cancers 45,46 and in congenital genetic diseases 14,15 were identified manually from the figures and the supplementary tables and figures in the original publications.”
Self-citationDiaz, G. M., Palencia, P. S., & Leapman, M. (2025) · Journal of Urologic Oncology · doi:10.22465/juo.255000120006 · Cited by 5
“While androgen deprivation therapy treatments can interfere with the AR pathway early in the disease course, this subtype of PCa often becomes resistant to this treatment and progresses to castration resistance prostate cancer (CRPC) [26,27].”
The MYH9 Cytoskeletal Protein Is a Novel Corepressor of Androgen Receptors
Liu, C., Liao, Z., Duan, X., Pan, Y., Kong, P., Tao, Z., & Liu, W. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.641496 · Cited by 5
“We describe herein results showing that compared with androgen-dependent prostate cancer (ADPC) cells, AR nuclear translocation capability is enhanced in androgen-independent prostate cancer (AIPC) cells.”
BackgroundInfluentialMuñoz‐Barrera, A., Rubio‐Rodríguez, L. A., Usera, A. D.-D., Jáspez, D., Lorenzo-Salazar, J. M., González‐Montelongo, R., García‐Olivares, V., & Flores, C. (2022) · Life · doi:10.3390/life12111939 · Cited by 7
Prognostic and clinicopathological value of CDK12 mutation in prostate cancer: a meta-analysis
Zhang, W., Zhou, L., & Di, J. (2023) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2023.2168647 · Cited by 5
“Recent studies show that the inactivation of CDK12 is associated with tandem duplication phenotype [25,31], leading to high copynumber gains of prostate cancer-relevant oncogenes (e.”
BackgroundRepertoire and clinical hierarchy of AR locus alterations in castration-resistant prostate cancer
Virtanen, T., Kwan, E. M., Parekh, K., Bacon, J. V. W., Huang, C.-C. F., Yu, I. P. L., Ryyppö, L., Bernales, C. Q., Donnellan, G., Tam, C. S. L., et al. (2025) · Annals of Oncology · doi:10.1016/j.annonc.2025.10.1236 · Cited by 5
Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis
Dsouza, J. M., Sayar, E., Schweizer, M. T., Harmon, S. A., Morrissey, C. M., Beltran, H., Nelson, P. S., Liang Cheng, C., Ding, C. C., & Haffner, M. C. (2025) · Histopathology · doi:10.1111/his.70033 · Cited by 4
Self-citationGuo, J., Wei, Z., Jia, T., Wang, L., Nama, N., Liang, J., Liao, X., Liu, X., Gao, Y., Liu, X., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04429-4 · Cited by 4
Liu, Q., Zhou, H., Wang, Y., Gui, J., Yang, D., Sun, J., Ge, D., Wu, S., Liu, Q., Zhu, L., et al. (2023) · Translational Oncology · doi:10.1016/j.tranon.2023.101830 · Cited by 4
“Although many therapeutic methods have been developed, castration-resistant prostate cancer (CRPC), which occurs after long-term androgen deprivation therapy, presents a major difficulty in treating CRPC patients due to its near incurability [5 – 7].”
BackgroundCompromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase
Pallasaho, S., Gondane, A., Kutz, J., Liang, J., Yalala, S., Duveau, D. Y., Pospiech, H., Thomas, C. J., Loda, M. F., & Itkonen, H. M. (2024) · Glycobiology · doi:10.1093/glycob/cwae081 · Cited by 4
Laere, B. D., Crippa, A., Mortezavi, A., Ghysel, C., Rajan, P., Eklund, M., Wyatt, A. W., Dirix, L. Y., Ost, P., Grönberg, H., et al. (2021) · Cancers · doi:10.3390/cancers13071588 · Cited by 4
“This was markedly higher in the CORE/PROBIO cohort as a result of the intronic sequencing performed for the CORE/PROBIO patients, enabling the detection of GSRs [11].”
MethodInfluentialLinked-read based analysis of the medulloblastoma genome
Zwaig, M., Johnston, M. J. G., Lee, J. J. Y., Farooq, H., Gallo, M., Jabado, N., Taylor, M. D., & Ragoussis, J. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1221611 · Cited by 4
LRTK: a platform agnostic toolkit for linked-read analysis of both human genome and metagenome
Yang, C., Zhang, Z., Huang, Y., Xie, X., Liao, H., Xiao, J., Veldsman, W. P., Yin, K., Fang, X., & Zhang, L. (2024) · GigaScience · doi:10.1093/gigascience/giae028 · Cited by 3
Self-citationEvolution of the prostate cancer genome towards resistance
Lorenzin, F., & Demichelis, F. (2019) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2019.01 · Cited by 4
“Of note, copy number gain of a region upstream of the AR locus that is characterized by histone marks typically found in enhancers, can act independently of the AR locus amplification to increase AR expression levels in response to first-line ADT([18,33,34]).”
BackgroundInfluentialvan Dessel, L. F., van Riet, J., Smits, M., Zhu, Y., Hamberg, P., van der Heijden, M. S., Bergman, A. M., van Oort, I. M., de Wit, R., Voest, E. E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/546051 · Cited by 4
Hawley, J. R., Zhou, S., Arlidge, C., Grillo, G., Kron, K., Hugh-White, R., van der Kwast, T., Fraser, M. E., Boutros, P. C., Bristow, R. G., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.05.425333 · Cited by 4
Haplotype-aware single-cell multiomics uncovers functional effects of somatic structural variationPreprint
Jeong, H., Grimes, K., Bruch, P., Rausch, T., Hasenfeld, P., Sabarinathan, R., Porubskỳ, D., Herbst, S. A., Erarslan-Uysal, B., Jann, J.-C., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.11.468039 · Cited by 4
A genetic basis for cancer sex differences revealed in Xp11 translocation renal cell carcinomaPreprint
Achom, M., Sadagopan, A., Bao, C., McBride, F., Xu, Q., Konda, P., Tourdot, R. W., Li, J., Nakhoul, M., Gallant, D. S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.04.552029 · Cited by 4
Self-citationThe genetic evolution of acral melanomaPreprint
Wang, M., Fukushima, S., Sheen, Y., Ramelyte, E., Cruz‐Pacheco, N., Shi, C., Liu, S., Banik, I., Aquino, J. D., Acosta, M. S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.18.562802 · Cited by 4
Frank, S. B., Persse, T. W., Coleman, I., Bankhead, A., Li, D., Sarkar, N. D., Wilson, D., Rudoy, D., Vashisth, M., Galipeau, P., et al. (2024) · eLife · doi:10.7554/elife.100081 · Cited by 4
Self-citationLi, S., Song, K., Sun, H., Tao, Y., Huang, A. J. Y., Bhatia, V., Hanratty, B. P., Patel, R. A., Long, H. W., Morrissey, C. M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.12.637904 · Cited by 4
Self-citationAlterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance
Gao, S., Patten, N. D., & Cai, C. (2025) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2025.05.003 · Cited by 4
“At the similar time, Viswanathan et al. 75 examined mCRPC biopsies and cell-free DNA and uncovered multiple structural alterations in CRPC, including complex rearrangements at the AR locus.”
Dincman, T. A., Karam, J. A. Q., Giordano, A., Li, H., Drusbosky, L. M., Gourdin, T. S., Howe, P. H., & Lilly, M. B. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2023.1202277 · Cited by 3
The Bioinformatic Applications of Hi-C and Linked Reads
Jiang, L., Quail, M. A., Fraser-Govil, J., Wang, H., Shi, X., Oliver, K., Gómez, E., Yang, F., & Ning, Z. (2024) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzae048 · Cited by 3
The role of CDK12 in tumor biology
Dzimková, M., Procházková, J., Klát, J., & Kohoutek, J. (2020) · Klinicka onkologie · doi:10.14735/amko2020260 · Cited by 3
Peña‐Pérez, L., Frengen, N. S., Hauenstein, J., Gran, C., Gustafsson, C., Eisfeldt, J., Kierczak, M., Taborsak-Lines, F., Olsen, R., Wallblom, A., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006720 · Cited by 4
Zaalberg, A., Pottendorfer, E., Zwart, W. T., & Bergman, A. M. (2024) · Cancers · doi:10.3390/cancers16020294 · Cited by 3
Ma, L., & Han, X. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23932-8.00020-0 · Cited by 3
Chromosome Territories in Hematological Malignancies
de Lima, M. F., Lisboa, M. D. O., Terceiro, L. E. L., Pozzo, A. R., & Mai, S. (2022) · Cells · doi:10.3390/cells11081368 · Cited by 3
CDK13 Mutations Drive Melanoma via Accumulation of Prematurely Terminated TranscriptsPreprint
Insco, M. L., Abraham, B. J., Dubbury, S. J., Dust, S., Wu, C., Chen, K. Y., Liu, D., Ludwig, C. G., Bellaousov, S., Fabo, T., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/824193 · Cited by 3
“391 In vitro Kinase Assays: 392 Radioactive kinase reactions were performed using recombinant human CDK13 (694-1039) and 393 Cyclin K (1-300) proteins.”
MethodMutational signatures of complex genomic rearrangements in human cancerPreprint
Bao, L., Zhong, X., Yang, Y., & Yang, L. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.16.444385 · Cited by 3
Large tandem duplications in cancer result from transcription and DNA replication collisionsPreprint
Yang, Y., Badura, M. L., O’Leary, P. C., Delavan, H. M., Robinson, T. M., Egusa, E. A., Zhong, X., Swinderman, J. T., Li, H., Zhang, M., et al. (2023) · medRxiv · doi:10.1101/2023.05.17.23290140 · Cited by 3
CHD1 status drives divergent metabolic pathways in SPOP-mutant prostate cancer
Orme, J. J., Antonarakis, E. S., & Dehm, S. M. (2025) · Nature Cancer · doi:10.1038/s43018-025-00959-6 · Cited by 2
Self-citationCheng, L., You, C., Ma, L., Liu, S., Lao, Y., Guan, X., Wang, W., Xiao, X., Tao, Y., & Dong, Z. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112163 · Cited by 2
Pandurangan, T., Zeleke, S. T., Iermolaieva, A., Ghosh, P., Mosior, J., Sun, L., Grassie, D., Schmitz, M., Kalaga, M. N., Albritton, W., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02086 · Cited by 2
Chen, Y., He, K., Qu, W., Ma, L., Su, X., Liu, X., Kang, Z., Li, F., Yan, J., Wang, Z., et al. (2026) · European Journal of Cancer · doi:10.1016/j.ejca.2026.116667 · Cited by 2
Evaluation of novel treatments for metastatic castration-resistant prostate cancer
Güner, G., & Arslan, Ç. (2026) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2026.2652456 · Cited by 2
“Approximately 85% of CRPC tumors harbor genetic alterations in the AR gene or its enhancer region, including amplifications, ligand-binding domain (LBD) mutations, and constitutively active splice variants such as AR-V7 [6].”
Advances in systemic therapies for advanced prostate cancer
Childs, D. S., Hahn, A. W., Ravi, P. K., & Orme, J. J. (2026) · BMJ · doi:10.1136/bmj-2025-085211 · Cited by 2
Latest progress in molecular biology and treatment in genitourinary tumours
del Alba, A. G., Arranz, J. Á., Joaquim Bellmunt, B., Maroto, P., Calvo, O. F., Valderrama, B. P., González‐Billalabeitia, E., Méndez-Vidal, M. J., Cassinello, J., Romero-Laorden, N., et al. (2020) · Clinical & Translational Oncology · doi:10.1007/s12094-020-02373-z · Cited by 2
Capped nascent RNA sequencing reveals novel therapy-responsive enhancers in prostate cancerPreprint
Cotter, K. A., Shah, S. R., Paramo, M. I., Lou, S., Li, Y., Rubin, P. D., Chen, Y., Gerstein, M., Rubin, M. A., & Yu, H. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.08.487666 · Cited by 2
“For example, upwards of 80% of samples were found to have a duplication of a region upstream of AR, which was then shown to be a previously unidentified enhancer(Quigley et al., 2018; Takeda et al., 2018; Viswanathan et al., 2018).”
BackgroundChromatin interaction maps identify oncogenic targets of enhancer duplications in cancerPreprint
Song, Y., Li, F., Wang, S., Wang, Y., Lai, C., Chen, L., Jiang, N., Li, J., Chen, X., Bailey, S. D., et al. (2024) · Genome Research · doi:10.1101/gr.278418.123 · Cited by 2
Yaragani, M., Yadlapalli, P., Raghavan, S. S., Giridhar, T., Mandava, V. B. R., Singh, R. V., Kottapalli, R. P., & Saravanan, C. (2022) · Chemical Biology & Drug Design · doi:10.1111/cbdd.14151 · Cited by 1
“Chronic use of these antagonists, on the contrary, frequently leads to the development of resistance, a disorder known as castration- resistant prostate cancer (CRPC) (Schweizer & Yu, 2015; Viswanathan et al., 2018).”
BackgroundLi, H., Luo, J., Liang, H., Yanfeng, B., Liu, J., Wei, T., Wang, L., Guo, H., Xia, D., Huang, H., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-25-1761 · Cited by 1
Lee, H., Ho, J.-N., Song, S. H., Oh, J. J., Huh, J. S., Kim, H.-M., Kim, K. H., Kim, S., & Byun, S.-S. (2025) · The World Journal of Men s Health · doi:10.5534/wjmh.250093 · Cited by 1
“The previous study by Viswanathan et al [28] found that the CRPC demonstrated higher rate of higher rate of complex rearrangement of the androgen receptor than primary PCa, possibly associated with CDK12 inactivation with enhanced tandem duplicator phenotype.”
Regulation of androgen receptor expression by enhancer elements in prostate cancer
Khadka, S., Jeon, H., Hussain, A., & Qi, J. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01624-9 · Cited by 1
Naga, S. P., Slootbeek, P. H. J., Tolmeijer, S. H., Gilissen, C., Ligtenberg, M. J. L., Mehra, N., & de Voer, R. M. (2026) · JCO Clinical Cancer Informatics · doi:10.1200/cci-25-00240 · Cited by 1
Metadata
- Authors
- Viswanathan, S. R., Ha, G., Hoff, A. M., Wala, J. A., Carrot-Zhang, J., Whelan, C. W., Haradhvala, N. J., Freeman, S. S., Reed, S. C., Rhoades, J., Polak, P., Cipicchio, M., Wankowicz, S. A., Wong, A., Kamath, T., Zhang, Z., Gydush, G. J., Rotem, D., Love, J. C., Getz, G., Gabriel, S., Zhang, C.-Z., Dehm, S. M., Nelson, P. S., Van Allen, E. M., Choudhury, A. D., Adalsteinsson, V. A., Beroukhim, R., Taplin, M.-E., & Meyerson, M.
- Affiliations
- Broad Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- Dana-Farber Cancer Institute (US)
- University of Minnesota (US)
- Fred Hutch Cancer Center (US)
- Harvard University (US)
- Corresponding author
- Meyerson, Matthew
- ORCID
- Viswanathan, Srinivas R.
- Ha, Gavin
- Hoff, Andreas M.
- Wala, Jeremiah A.
- Whelan, Christopher W.
- Haradhvala, Nicholas J.
- Freeman, Samuel S.
- Reed, Sarah C.
- Rhoades, Justin
- Polak, Paz
- Cipicchio, Michelle
- Wankowicz, Stephanie A.
- Wong, Alicia
- Kamath, Tushar
- Zhang, Zhenwei
- Rotem, Denisse
- Love, J. Christopher
- Getz, Gad
- Gabriel, Stacey
- Zhang, Cheng-Zhong
- Dehm, Scott M.
- Nelson, Peter S.
- Choudhury, Atish D.
- Adalsteinsson, Viktor A.
- Beroukhim, Rameen
- Taplin, Mary-Ellen
- Meyerson, Matthew
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 174
- Issue
- 2
- Pages
- 433-447.e19
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6046279
- OpenAlex
- W2807985734
- Cited by
- 365
- References
- 65
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 47 · 2023: 48 · 2022: 59 · 2021: 51 · 2020: 53 · 2019: 45 · 2018: 16
- FWCI
- 31.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Department of Defense (W81XWH-17-1-0358)
- Prostate Cancer Foundation Young Investigator Award
- Canadian Institutes of Health Research (MFE-140389)
- Norwegian Cancer Society (PR-2007-0166)
- NIH (K08 CA188615, R01CA174777, P01CA163227, NIH R01 CA215489)
- NCI (R35 CA197568)
- PCF-V Foundation
- Movember
- PCF
- Gerstner Family Foundation
- Prostate SPORE (P50CA097186)
- Fund for Innovation in Cancer Informatics
- American Cancer Society Research Professorship
- American Association for Cancer Research (SU2C-AACR-DT0712)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- castration-resistant prostate cancer, metastatic prostate cancer, tandem duplication, genome rearrangement, cell-free DNA, linked-read sequencing
- MeSH terms
- Whole Genome Sequencing, Aged, Anilides, Enhancer Elements, Genetic, Haplotypes, Humans, Male, Middle Aged, Neoplasm Metastasis, Phenotype, Pyridines, Receptors, Androgen, Gene Rearrangement, Genes, myc, Prostate-Specific Antigen, Cyclin-Dependent Kinases, Gene Duplication, Protein Kinase Inhibitors, PTEN Phosphohydrolase, Genetic Loci, Prostatic Neoplasms, Castration-Resistant
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