Evidence map›Paper›PMID 40671039›Full record

ArticleMobile DNA2025

In-depth analysis of endogenous retrovirus expression in glioblastoma.

Daniel A Murimi-Worstell, Irene B Murimi-Worstell, Farrah M Roy, Aidan Burn, Michael Freeman, Ralph B Puchalski, John M Coffin

Abstract read
In one paragraph

Article in Mobile DNA, 2025. 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
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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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Daniel A Murimi-WorstellProgram in Molecular Biology and Microbiology, Graduate School of Biomedical Sciences, Tufts University, 150 Harrison Avenue. (617), Boston, MA, 636-6528, United States of America.
Irene B Murimi-WorstellDepartment of Pharmaceutical Economics and Policy, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, United States of America.
Farrah M RoyImmuneering Corporation, Cambridge, MA, United States of America.
Aidan BurnProgram in Genetics, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States of America.
Michael FreemanProgram in Molecular Biology and Microbiology, Graduate School of Biomedical Sciences, Tufts University, 150 Harrison Avenue. (617), Boston, MA, 636-6528, United States of America.
Ralph B PuchalskiBen and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA, United States of America.
John M CoffinProgram in Molecular Biology and Microbiology, Graduate School of Biomedical Sciences, Tufts University, 150 Harrison Avenue. (617), Boston, MA, 636-6528, United States of America. john.coffin@tufts.edu.

Funding

Retrovirus Evolution and CancerR35CA200421 · NCI · TUFTS UNIVERSITY BOSTON · PI COFFIN, JOHN M · 2016 to 2022
$6.5M
RETROVIRUS EVOLUTIONR01CA089441 · NCI · TUFTS UNIVERSITY BOSTON · PI COFFIN, JOHN M · 2001 to 2005
$3.0M
Human endogenous provirus inhibition of HIV replicationR01AI184043 · NIAID · TUFTS UNIVERSITY BOSTON · PI JOHN M COFFIN · 2024 to 2026
$2.1M
Molecular Genetics of Basic Cell FunctionT32GM139772 · NIGMS · TUFTS UNIVERSITY BOSTON · PI Andrew Camilli · 2022 to 2026
$1.3M
NCI NIH HHS R01 CA089441NIAID NIH HHS R01 AI184043NIGMS NIH HHS T32 GM139772US NIH R35 CA 200421
6 · The paper itself

Abstract

backgroundHuman endogenous retroviruses (HERVs) are remnants of ancient viral infections and comprise 6-8% of the human genome. Their biological functions in cancer remain poorly understood, especially in glioblastoma, the most common and deadly primary brain cancer in adults. Prior studies on HERV expression in glioblastoma have yielded conflicting results. Here, we employed orthogonal computational pipelines to address these limitations.

resultsLocus-specific analysis revealed marked heterogeneity of transcription among HERVs within the same clade. We found that individual HERV proviruses are more than twice as likely to be underexpressed in glioblastoma than overexpressed and that most differentially expressed HERVs are exonized within transcripts. These HERVs are enriched in the 3'-terminal exons of transcripts, associated with alternative polyadenylation and contribute conserved polyadenylation signals. We identified HERV expression patterns associated with glioblastoma subtypes and anatomic features. We also identified three proviruses or proviral fragments of particular interest including one associated with survival and one exonized within a currently unannotated cancer-specific transcript. Among the most recently integrated clade of HERVs, excluding solo-LTRs, only the HML-2 provirus at 1q22 is overexpressed in glioblastoma. We report previously undescribed transcripts incorporating this provirus that may encode several proteins.

conclusionsThis study represents the first systematic exploration of the heterogeneity of HERV expression between anatomic features of any cancer. It shows that exaptation of HERV polyadenylation signals and HERV-associated APA are widespread in the human transcriptome and identifies critical structural information regarding the HML-2 1q22 provirus transcript, which has been the focus of several recent analyses. Our findings underscore the importance of locus-specific and anatomic feature-specific HERV analysis and suggest structural and functional roles for HERVs in glioblastoma-associated transcripts.

Indexed as

AnatomicAPABiomarkerExaptationFeatureGlioblastomaHERVHeterogeneityHML-2Polyadenylation

Identifiers

PMID40671039
PMCPMC12265125

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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.