Evidence map›Paper›PMID 16651410›Full record

ArticleCancer research2006

Functional gene expression analysis uncovers phenotypic switch in aggressive uveal melanomas.

Michael D Onken, Justis P Ehlers, Lori A Worley, Jun Makita, Yoshifumi Yokota, J William Harbour

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

Article in Cancer research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00406120 (Validation of a Molecular Test for Predicting Metastasis in Patients With Uveal Melanoma), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
11.5field-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.

NCT00406120 withdrawnnot on this mapstarted 2007, after this paper: background citation

Validation of a Molecular Test for Predicting Metastasis in Patients With Uveal Melanoma

TypeobservationalSponsorWashington University School of MedicineRan2007 to 2010Enrolled0ConditionsUveal Neoplasms, Choroid Neoplasms, Iris NeoplasmsArmsFine needle aspiration biopsy
3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. BAP1 Loss Affords Lipotoxicity Resistance in Uveal Melanoma.Pigment cell & melanoma research · 2025
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25 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Michael D OnkenDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Justis P Ehlers
Lori A Worley
Jun Makita
Yoshifumi Yokota
J William Harbour
University of Fukui · JPWashington University in St. Louis · US

Funding

MOLECULAR PREDICTIVE TESTING IN OCULAR MELANOMAR01CA125970 · NCI · WASHINGTON UNIVERSITY · PI CORREA, ZELIA MARIA, HARBOUR, JAMES WILLIAM · 2006 to 2021
$4.9M
THE ROLE OF RB IN THE RETINA &OTHER TISSUESR01EY013169 · NEI · WASHINGTON UNIVERSITY · PI HARBOUR, JAMES WILLIAM · 2000 to 2009
$3.0M
NCI NIH HHS R01 CA125970NEI NIH HHS R01 EY013169NEI NIH HHS R01 EY13169
6 · The paper itself

Abstract

Microarray gene expression profiling is a powerful tool for generating molecular cancer classifications. However, elucidating biological insights from these large data sets has been challenging. Previously, we identified a gene expression-based classification of primary uveal melanomas that accurately predicts metastatic death. Class 1 tumors have a low risk and class 2 tumors a high risk for metastatic death. Here, we used genes that discriminate these tumor classes to identify biological correlates of the aggressive class 2 signature. A search for Gene Ontology categories enriched in our class-discriminating gene list revealed a global down-regulation of neural crest and melanocyte-specific genes and an up-regulation of epithelial genes in class 2 tumors. Correspondingly, class 2 tumors exhibited epithelial features, such as polygonal cell morphology, up-regulation of the epithelial adhesion molecule E-cadherin, colocalization of E-cadherin and beta-catenin to the plasma membrane, and formation of cell-cell adhesions and acinar structures. One of our top class-discriminating genes was the helix-loop-helix inhibitor ID2, which was strongly down-regulated in class 2 tumors. The class 2 phenotype could be recapitulated by eliminating Id2 in cultured class 1 human uveal melanoma cells and in a mouse ocular melanoma model. Id2 seemed to suppress the epithelial-like class 2 phenotype by inhibiting an activator of the E-cadherin promoter. Consequently, Id2 loss triggered up-regulation of E-cadherin, which in turn promoted anchorage-independent cell growth, a likely antecedent to metastasis. These findings reveal new roles for Id2 and E-cadherin in uveal melanoma progression, and they identify potential targets for therapeutic intervention.

Indexed as

AnimalsCadherinsCell Growth ProcessesCell Line, TumorGene Expression ProfilingHumansInhibitor of Differentiation Protein 2MelanomaMiceMice, TransgenicTransfectionUveal NeoplasmsCadherinsID2 protein, humanInhibitor of Differentiation Protein 2

Identifiers

PMID16651410
PMCPMC5407689
OpenAlexW1996119746

What OpenQuestion holds

Textmetadata
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.