Evidence map›Paper›PMID 40024557›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2025

PRAME Expression in Melanoma is Negatively Regulated by TET2-Mediated DNA Hydroxymethylation.

Rui Fang, Tuulia Vallius, Arianna Zhang, Devon Van Cura, Francisco Alicandri, Grant Fischer, Elizabeth Draper, Shuyun Xu, Roxanne Pelletier, Justina Wang and 5 more

Abstract read
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Rui FangDivision of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Tuulia ValliusLaboratory of Systems Pharmacology, Harvard Medical School, Harvard Program in Therapeutic Science, Boston, Massachusetts; Ludwig Center at Harvard Medical School, Boston, Massachusetts.
Arianna ZhangDepartment of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Devon Van CuraDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
Francisco AlicandriDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Grant FischerDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Elizabeth DraperDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Shuyun XuDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Roxanne PelletierLaboratory of Systems Pharmacology, Harvard Medical School, Harvard Program in Therapeutic Science, Boston, Massachusetts; Ludwig Center at Harvard Medical School, Boston, Massachusetts.
Justina WangDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Anna MandinovaCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Harvard Stem Cell Institute, Cambridge, Massachusetts.
Igor KatsyvDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Medical School, Harvard Program in Therapeutic Science, Boston, Massachusetts; Ludwig Center at Harvard Medical School, Boston, Massachusetts; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts. Electronic address: peter_sorger@hms.harvard.edu.
George F MurphyDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: gmurphy@bwh.harvard.edu.
Christine G LianDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: cglian@bwh.harvard.edu.

Funding

Pre-cancer atlases of cutaneous and hematologic origin (PATCH Center)U2CCA233262 · NCI · HARVARD MEDICAL SCHOOL · PI SANTAGATA, SANDRO · 2018 to 2023
$8.7M
CTSA Postdoctoral T32 at Tufts UniversityT32TR004418 · NCATS · TUFTS UNIVERSITY BOSTON · PI DAVID M KENT · 2023 to 2026
$2.2M
NCATS NIH HHS T32 TR004418NCI NIH HHS U2C CA233262
6 · The paper itself

Abstract

Preferentially expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of The Cancer Genome Atlas and Genotype-Tissue Expression databases confirmed a negative relationship between TET2 and PRAME messenger RNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared with nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis.

Indexed as

Antigens, NeoplasmDNA-Binding ProteinsDNA MethylationGene Expression Regulation, NeoplasticMelanomaProto-Oncogene ProteinsSkin Neoplasms5-MethylcytosineCell Line, TumorDioxygenasesHumans5-hydroxymethylcytosine5-MethylcytosineAntigens, NeoplasmDioxygenasesDNA-Binding ProteinsPRAME protein, humanProto-Oncogene ProteinsTET2 protein, human5-hydroxymethylcytosinebiomarkersepigeneticsmelanomapreferentially expressed antigen in melanomaten-eleven translocation 2

Identifiers

PMID40024557
PMCPMC12509701

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Registered trials

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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.