Evidence map›Paper›PMID 28961847›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2017

Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters.

M Linch, G Goh, C Hiley, Y Shanmugabavan, N McGranahan, A Rowan, Y N S Wong, H King, A Furness, A Freeman and 24 more

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

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02022371 (Prostate Cancer Genomic Heterogeneity), which is not on this map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.3field-weighted citation impact, top 3% 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.

NCT02022371 phase1 / phase2completednot on this map

Prostate Cancer Genomic Heterogeneity

TypeinterventionalSponsorUniversity College London HospitalsRan2014 to 2016Enrolled50ConditionsPROSTATE CANCERArmsTargeted biopsies of the prostate
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 62 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Immunotherapy in Advanced Prostate Cancer-Light at the End of the Tunnel?International journal of molecular sciences · 2022
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Inflammation-Induced Tumorigenesis and Metastasis.International journal of molecular sciences · 2021
    Review
  18. Characterizing CDK12-Mutated Prostate Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  19. Prostate cancer: Therapeutic prospect with herbal medicine.Current research in pharmacology and drug discovery · 2021
    Review
  20. Prostate carcinogenesis: inflammatory storms.Nature reviews. Cancer · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 9 institutions in 4 countries.

M LinchTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
G GohTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Bill Lyons Informatics Centre, UCL Cancer Institute, London, UK.
C HileyDivision of Cancer Studies, King's College London, London, UK;; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
Y ShanmugabavanDivision of Surgery and Interventional Science, University College London, London, UK.
N McGranahanTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
A RowanTranslational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
Y N S WongTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Cancer Immunology Unit, UCL Cancer Institute, London, UK;; Research Department of Haematology, UCL Cancer Institute, London, UK.
H KingTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK.
A FurnessCancer Immunology Unit, UCL Cancer Institute, London, UK;; Research Department of Haematology, UCL Cancer Institute, London, UK.
A FreemanDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK.
J LinaresDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK.
A AkarcaDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK.
J HerreroBill Lyons Informatics Centre, UCL Cancer Institute, London, UK.
R RosenthalTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Bill Lyons Informatics Centre, UCL Cancer Institute, London, UK.
N HarderDefiniens AG, Munich, Germany.
G SchmidtDefiniens AG, Munich, Germany.
G A WilsonTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
N J BirkbakTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
R MitterDepartment of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK.
S DentroCancer Genomics Laboratory, The Francis Crick Institute, London, UK;; Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge, UK.
P CathcartThe Urology Centre, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
M AryaDivision of Surgery and Interventional Science, University College London, London, UK;; Department of Urology, UCLH NHS Foundation Trust, London, UK.
E JohnstonCentre for Medical Imaging, Universtiy College London, London, UK.
R ScottDivision of Surgery and Interventional Science, University College London, London, UK.
M HungDivision of Surgery and Interventional Science, University College London, London, UK.
M EmbertonDivision of Surgery and Interventional Science, University College London, London, UK;; Department of Urology, UCLH NHS Foundation Trust, London, UK.
G AttardCentre for Evolution and Cancer, The Institute of Cancer Research, London, UK;; Department of Medical Oncology, Royal Marsden Hospital, London, UK.
Z SzallasiCentre for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;; Computational Health Informatics Program (CHIP), Harvard Medical School, Boston, USA;; MTA-SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary.
S PunwaniCentre for Medical Imaging, Universtiy College London, London, UK.
S A QuezadaCancer Immunology Unit, UCL Cancer Institute, London, UK;; Research Department of Haematology, UCL Cancer Institute, London, UK.
T MarafiotiDepartment of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK.
M GerlingerCentre for Evolution and Cancer, The Institute of Cancer Research, London, UK;; Department of Medical Oncology, Royal Marsden Hospital, London, UK.
H U AhmedDivision of Surgery and Interventional Science, University College London, London, UK;; Division of Surgery, Department of Surgery and Cancer, Imperial College London, UK;; Department of Urology, Imperial College Healthcare NHS Trust, London, UK. Electronic address: hashim.ahmed@imperial.ac.uk.
C SwantonTranslational Cancer Therapeutics Laboratory, UCL Cancer Institute, London, UK;; Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK;; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK;. Electronic address: charles.swanton@crick.ac.uk.
University College London · GBCRUK Lung Cancer Centre of Excellence · GBThe Francis Crick Institute · GBUniversity College London Hospitals NHS Foundation Trust · GBInstitute of Cancer Research · GBGuy's and St Thomas' NHS Foundation Trust · GBImperial College Healthcare NHS Trust · GBTechnical University of Denmark · DKWellcome Sanger Institute · GB

Funding

Cancer Research UK 18377Cancer Research UK 20764Cancer Research UK 22744Department of Health 09/22/67Medical Research Council G0701302Medical Research Council G1002509Prostate Cancer UK PG13-025Wellcome Trust FC001169
6 · The paper itself

Abstract

backgroundIntratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. PATIENTS AND

methodsForty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification.

resultsWe demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion.

conclusionsThe PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. CLINICAL TRIALS.GOV IDENTIFIER: NCT02022371.

Indexed as

BiopsyEpitopes, B-LymphocyteGene DosageGenetic HeterogeneityHumansLymphocytes, Tumor-InfiltratingMaleMutationNeoplasm MetastasisProstatic NeoplasmsRisk FactorsT-LymphocytesT-Lymphocyte SubsetsWnt Signaling PathwayEpitopes, B-Lymphocyteintratumoural heterogeneitymismatch repairneoepitopesprostate cancertumour infiltrating lymphocyteswnt signalling

Identifiers

PMID28961847
PMCPMC5815564
OpenAlexW2738309976

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.