Evidence map›Paper›PMID 39091741›Full record

ArticlebioRxiv : the preprint server for biology2024

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, Igor Katsyv and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Rui FangDepartment of Medicine, Brigham and Women's Hospital; Harvard Medical School, Boston MA 02115.
Tuulia ValliusLaboratory of Systems Pharmacology, Harvard Medical School, Boston MA 02115 Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.ORCID 0000-0002-3006-4887
Arianna ZhangDepartment of Dermatology, Brigham and Women's Hospital; Harvard Medical School, Boston MA 02115.
Devon Van CuraDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge MA 02138.
Francisco AlicandriDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Grant FischerDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Elizabeth DraperDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Shuyun XuDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Roxanne PelletierLaboratory of Systems Pharmacology, Harvard Medical School, Boston MA 02115 Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.ORCID 0000-0002-1957-5483
Igor KatsyvDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Peter K SorgerLaboratory of Systems Pharmacology, Harvard Medical School, Boston MA 02115 Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.ORCID 0000-0002-3364-1838
George F MurphyDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.
Christine G LianDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115.ORCID 0000-0003-4626-1612

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 TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to 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. Teaser: Melanoma biomarker PRAME expression is negatively regulated epigenetically by TET2-mediated DNA hydroxymethylation.

Indexed as

5-hmCbiomarkersepigeneticsmelanomaPRAMETET2

Identifiers

PMID39091741
PMCPMC11291125

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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.