The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
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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Genomic correlates of clinical outcome in advanced prostate cancer
Abida, W., Cyrta, J., Heller, G., Prandi, D., Armenia, J., Coleman, I., Cieslik, M., Benelli, M., Robinson, D., Van Allen, E. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902651116 · Cited by 1,372
Self-citationPan-cancer whole-genome analyses of metastatic solid tumours
Priestley, P., Baber, J., Lolkema, M. P., Steeghs, N., de Bruijn, E., Shale, C., Duyvesteyn, K., Haidari, S., van Hoeck, A., Onstenk, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1689-y · Cited by 1,106
Structural variation in the sequencing era
Ho, S. S., Urban, A. E., & Mills, R. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0180-9 · Cited by 630
“Part b adapted with permission from ref.(153), Elsevier.”
BackgroundAndrogen receptor splice variant-7 expression emerges with castration resistance in prostate cancer
Sharp, A., Coleman, I. M., Yuan, W., Sprenger, C. C. T., Dolling, D. I., Rodrigues, D. N., Russo, J. W., Figueiredo, I., Bertan, C. M., Seed, G., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci122819 · Cited by 403
Self-citationThe DNA methylation landscape of advanced prostate cancer
Zhao, S. G., Chen, W. S., Li, H., Foye, A., Zhang, M., Sjöström, M., Aggarwal, R. R., Playdle, D., Liao, A., Alumkal, J. J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0648-8 · Cited by 357
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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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