Evidence map›Paper›PMID 29909985›Full record

ArticleCell2018

Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing.

Srinivas R Viswanathan, Gavin Ha, Andreas M Hoff, Jeremiah A Wala, Jian Carrot-Zhang, Christopher W Whelan, Nicholas J Haradhvala, Samuel S Freeman, Sarah C Reed, Justin Rhoades and 21 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04015622 (A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone), which is not on this map. Cited by 231 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed, 1 pooled it
32.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04015622 phase2active not recruitingnot on this mapstarted 2020, after this paper: background citation

A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone

TypeinterventionalSponsorBritish Columbia Cancer AgencyRan2020 to 2026Enrolled100ConditionsMetastatic Castration-Resistant Prostate Cancer (mCRPC)ArmsEnzalutamide, Docetaxel
3 · Its place in the literature

Who cites it

231 citing papers in PubMed, 1 synthesis or guideline pooled it, 376 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Single-Cell Circulating Tumor Cell Analysis Reveals Genomic Instability as a Distinctive Feature of Aggressive Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
    Review
  9. AR and Beyond: ctDNA Maps Resistance Evolution in mCRPC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

171 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 9 institutions in 2 countries.

Srinivas R ViswanathanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Gavin HaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Andreas M HoffCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Jeremiah A WalaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Jian Carrot-ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Christopher W WhelanHarvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas J HaradhvalaCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Samuel S FreemanCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Sarah C ReedCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Justin RhoadesCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Paz PolakIcahn School of Medicine at Mount Sinai, New York, NY, USA.
Michelle CipicchioCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stephanie A WankowiczDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alicia WongCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Tushar KamathCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Zhenwei ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Gregory J GydushCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Denisse RotemCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
PCF/SU2C International Prostate Cancer Dream Team
J Christopher LoveCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Gad GetzCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Stacey GabrielCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cheng-Zhong ZhangCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Cambridge, MA, USA.
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Peter S NelsonDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Atish D ChoudhuryDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Viktor A AdalsteinssonCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Koch Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
Rameen BeroukhimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Brigham and Women's Hospital, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mary-Ellen TaplinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Matthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA. Electronic address: matthew_meyerson@dfci.harvard.edu.
Broad Institute · USHarvard University · USDana-Farber Cancer Institute · USBrigham and Women's Hospital · USFred Hutch Cancer Center · USIcahn School of Medicine at Mount Sinai · USMassachusetts General Hospital · USOslo University Hospital · NOUniversity of Minnesota Medical Center · US

Funding

TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1M
Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI LODA, MASSIMO · 2002 to 2017
$36.2M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Steven P. Balk · 2013 to 2026
$25.0M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
NKX2-1 Enhancer Amplification and Lineage Addiction in Lung AdenocarcinomaR35CA197568 · NCI · DANA-FARBER CANCER INST · PI Matthew L. Meyerson · 2015 to 2026
$12.4M
Genetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9M
AR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9M
MYB family alterations in pediatric gliomasR01CA215489 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.8M
Resistance to Emerging Androgen Deprivation Therapies in Prostate CancerK08CA188615 · NCI · DANA-FARBER CANCER INST · PI VAN ALLEN, ELIEZER M · 2014 to 2017
$708k
CIHR MFE-140389NCI NIH HHS K08 CA188615NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA090381NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA215489NCI NIH HHS R35 CA197568NCI NIH HHS T32 CA009172NHGRI NIH HHS T32 HG002295
6 · The paper itself

Abstract

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.

Indexed as

Whole Genome SequencingAgedAnilidesCyclin-Dependent KinasesEnhancer Elements, GeneticGene DuplicationGene RearrangementGenes, mycGenetic LociHaplotypesHumansMaleMiddle AgedNeoplasm MetastasisPhenotypeProstate-Specific AntigenAnilidescabozantinibCDK12 protein, humanCyclin-Dependent KinasesProstate-Specific AntigenProtein Kinase InhibitorsPTEN PhosphohydrolasePTEN protein, humanPyridinesReceptors, Androgenandrogen receptorcastration-resistant prostate cancerCDK12cell-free DNAenhancerlinked read whole-genome sequencingMYCnon-coding cancer genomestructural variantstandem duplicator phenotype

Identifiers

PMID29909985
PMCPMC6046279
OpenAlexW2807985734

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.