ArticleCell2018
Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer.
2 registry-linked trialsOpen access · bronzeAbstract read
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 2 registered trials, which are not on this map. Cited by 351 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
351citing papers in PubMed, 2 pooled it
26.7field-weighted citation impact, top 1% of its field
What it found
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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.
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
Nivolumab as a Non-Castrating Therapy for MMR-deficient and CDK12- Altered Prostate Cancer With PSA Recurrence After Local Therapy
Who cites it
351 citing papers in PubMed, 2 syntheses or guidelines pooled it, 590 citations in OpenAlex.
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- BilT03: Phase 1b/2 multicenter trial of nivolumab with 5-fluorouracil and liposomal irinotecan for previously treated advanced biliary tract cancer.Med (New York, N.Y.) · 2025Trial
- Phase II trial of multi-kinase inhibitor ESK981 in patients with metastatic castration-resistant prostate cancer.Investigational new drugs · 2024Trial
- Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Accumulation of copy number alterations and clinical progression across advanced prostate cancer.Genome medicine · 2022Trial
- CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.Nature communications · 2022Trial
- Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial.Nature medicine · 2022Trial
- Review
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Immunoediting and precision biomarkers in prostate cancer: The emerging role of liquid biopsy, immune contexture and HLA genotype (Review).International journal of oncology · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Immune Spatial Organization Predicts Distant Metastasis Risk in Aggressive Localized Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- CDK12/13 Inhibition Induces DNA Hypomethylation and Sensitizes Cancer Cells to Compounds Targeting DNA-PK.Journal of cellular and molecular medicine · 2026Article
- Platinum-based chemotherapy in metastatic castration-resistant prostate cancer: a narrative review and dual stratification framework based on HRR genotype and aggressive-variant/neuroendocrine phenotype.International urology and nephrology · 2026Review
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Review
- Long-Read Haplotype Phasing Resolves Allelic Configuration as a Missing Layer of Precision Oncology.medRxiv : the preprint server for health sciences · 2026Article
291 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Yi-Mi WuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Marcin CieślikMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Robert J LonigroMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Pankaj VatsMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Melissa A ReimersDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Yu NingMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Lisha WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Lakshmi P KunjuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Navonil de SarkarDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Elisabeth I HeathDepartment of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
Jonathan ChouDepartment of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA.
Felix Y FengDepartment of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA; Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California at San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA 94143, USA.
Peter S NelsonDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Johann S de BonoCancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK; Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK.
Weiping ZouMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Bruce MontgomeryDepartment of Medicine, University of Washington, Seattle, WA 98109, USA; Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA 98109, USA.
Ajjai AlvaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
PCF/SU2C International Prostate Cancer Dream Team
Dan R RobinsonMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: danrobi@umich.edu.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: arul@umich.edu.
University of Michigan · USUniversity of California, San Francisco · USUniversity of Washington · USFred Hutch Cancer Center · USHoward Hughes Medical Institute · USRoyal Marsden NHS Foundation Trust · GBWayne State University · US
Funding
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6MMolecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4MSequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, PIENTA, KENNETH J. · 2013 to 2016
$7.8MDiscovery and qualification of transcriptomic biomarkers for the early detection of aggressive prostate cancerU01CA214170 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2016 to 2021
$3.3MImmune Impact on Cancer ChemoresistanceR01CA211016 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2017 to 2021
$3.0MEffector T Cell Trafficking in Ovarian CancerR01CA190176 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2015 to 2019
$2.6MHoward Hughes Medical InstituteNCI NIH HHS P50 CA097186NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA190176NCI NIH HHS R01 CA211016NCI NIH HHS T32 CA108462NCI NIH HHS U01 CA214170NHGRI NIH HHS UM1 HG006508
Abstract
Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication. CDK12 mutant cases are baseline diploid and do not exhibit DNA mutational signatures linked to defects in homologous recombination. CDK12 mutant cases are associated with elevated neoantigen burden ensuing from fusion-induced chimeric open reading frames and increased tumor T cell infiltration/clonal expansion. CDK12 inactivation thereby defines a distinct class of mCRPC that may benefit from immune checkpoint immunotherapy.
Indexed as
Antibodies, MonoclonalCell Line, TumorChemokine CCL21Cyclin-Dependent KinasesDNA RepairGene Expression Regulation, NeoplasticGenomic InstabilityHumansMaleMutation, MissenseNeoplasm StagingNuclear ProteinsPhenotypeProgrammed Cell Death 1 ReceptorProstateProstatic NeoplasmsAntibodies, MonoclonalCDK12 protein, humanChemokine CCL21Cyclin-Dependent KinasesNuclear ProteinsProgrammed Cell Death 1 ReceptorRepressor ProteinsRNA, Small InterferingSPOP protein, humanCDK12focal tandem duplicationsgene fusionsimmunotherapymetastatic castration-resistant prostate cancerneoantigens
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Registered trials
NCT04015622ClinicalTrials.gov
NCT04019964ClinicalTrials.gov
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.