Evidence map›Paper›PMID 29398457›Full record

ArticleEuropean urology focus2019

Genomic Heterogeneity Within Individual Prostate Cancer Foci Impacts Predictive Biomarkers of Targeted Therapy.

David J VanderWeele, Richard Finney, Kotoe Katayama, Marc Gillard, Gladell Paner, Seiya Imoto, Rui Yamaguchi, David Wheeler, Justin Lack, Maggie Cam and 11 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology focus, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
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  5. Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024
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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

21 authors at 4 institutions in 2 countries.

David J VanderWeeleLaboratory for Genitourinary Pathogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Department of Medicine, University of Chicago, Chicago, IL, USA. Electronic address: david.vanderweele@nih.gov.
Richard FinneyCenter for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Kotoe KatayamaHuman Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Marc GillardDepartment of Medicine, University of Chicago, Chicago, IL, USA; Department of Surgery, University of Chicago, Chicago, IL, USA.
Gladell PanerDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Seiya ImotoHuman Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Rui YamaguchiHuman Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
David WheelerCenter for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Justin LackCenter for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Maggie CamCenter for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Andrea PontierDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Yen Thi Minh NguyenLaboratory for Genitourinary Pathogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Kazuhiro MaejimaLaboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama City , Kanagawa, Japan.
Aya Sasaki-OkuLaboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama City , Kanagawa, Japan.
Kaoru NakanoLaboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama City , Kanagawa, Japan.
Hiroko TanakaHuman Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Donald Vander GriendDepartment of Surgery, University of Chicago, Chicago, IL, USA.
Michiaki KuboDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Mark J RatainDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Satoru MiyanoHuman Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Hidewaki NakagawaLaboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama City , Kanagawa, Japan.
University of Chicago · USNational Cancer Institute · USThe University of Tokyo · JPRIKEN Center for Integrative Medical Sciences · JP

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI THOMAS F GAJEWSKI · 1985 to 2026
$122.1M
Targeting FOXA1-downstream pathways: a novel therapeutic strategy for castration-resistant prostate cancerP50CA180995 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ABDULKADIR, SARKI A., HUSSAIN, MAHA H · 2015 to 2025
$19.9M
Multiregion sequencing of localized prostate cancerZIABC011719 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI VANDERWEELE, DAVID · 2016 to 2018
$274k
Evolution of prostate cancer genomeZIABC011770 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI VANDERWEELE, DAVID · 2017 to 2017
$43k
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011719Intramural NIH HHS ZIA BC011770NCI NIH HHS P30 CA014599NCI NIH HHS P50 CA180995
6 · The paper itself

Abstract

backgroundMost lethal prostate cancers progress from relapse of aggressive primary disease. Recently, the most significant advances in survival benefit from systemic therapy have come from moving the administration of therapy to an earlier disease state. There is movement toward using biomarkers from the intraprostatic index lesion to guide early systemic therapy.

objectiveTo determine the genomic heterogeneity, including the heterogeneity of predictive biomarkers, within the index focus of treatment-naïve prostate cancer. DESIGN, SETTING, AND

participantsTen patients with treatment-naïve prostate cancer underwent prostatectomy. DNA was extracted from 70 spatially distinct regions of the 10 index foci. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Single nucleotide mutations, small indels, and copy number changes were identified. Intrafocal genomic heterogeneity and heterogeneity of alterations that predict response to therapy was determined. RESULTS AND LIMITATIONS: Exome sequencing and copy number estimates demonstrate branched evolution with >75% of point mutations being subclonal, including numerous pathways associated with castrate-resistant prostate cancer. Seven of 10 patients harbor alterations in one of five genes that predict response to targeted therapies with survival benefit in prostate cancer. Within biomarker-positive cases, 25% of intraprostatic regions are biomarker negative, with discordance between intraprostatic regions and lymph node metastases.

conclusionsTreatment-naïve, nonmetastatic prostate cancer has marked intrafocal heterogeneity. Numerous alterations in pathways associated with castration-resistant prostate cancer are present in subclonal populations, including biomarkers predictive of response to targeted therapy. PATIENT SUMMARY: Untreated patients' tumors have alterations that predict response to targeted therapies, but the presence of a biomarker is dependent on what region of the tumor was evaluated.

Indexed as

AgedDNA, NeoplasmGenetic MarkersGenetic VariationHumansLymphatic MetastasisMaleMiddle AgedMolecular Targeted TherapyMutationNeoplasm GradingPrognosisProstateProstatectomyProstatic NeoplasmsSequence Analysis, DNADNA, NeoplasmGenetic MarkersClonal evolutionCopy number alterationExome sequencingGenomic heterogeneityMultiregion sequencingPredictive biomarkersProstate cancerSubclonal architectureTargeted therapy

Identifiers

PMID29398457
PMCPMC6586528
OpenAlexW2785933461

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.