Evidence map›Paper›PMID 40676699›Full record

ArticleGenome biology2025

Direct genetic transformation bypasses tumor-associated DNA methylation alterations.

Sara Hetzel, Eran Hodis, Elena Torlai Triglia, Alexander Kovacsovics, Kathleen Steinmann, Andreas Gnirke, Meiying Cui, Daniel McQuaid, Raha Weigert, Georg Pohl and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

18 authors.

Sara HetzelMax Planck Institute for Molecular Genetics, Berlin, Germany.
Eran HodisBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Elena Torlai TrigliaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexander KovacsovicsMax Planck Institute for Molecular Genetics, Berlin, Germany.
Kathleen SteinmannBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Andreas GnirkeBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Meiying CuiDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Daniel McQuaidDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Raha WeigertMax Planck Institute for Molecular Genetics, Berlin, Germany.
Georg PohlMax Planck Institute for Molecular Genetics, Berlin, Germany.
Mandar D MuzumdarDepartment of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
Serge LeyvrazCharité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany.
Ulrich KeilholzCharité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany.
Marie-Laure YaspoMax Planck Institute for Molecular Genetics, Berlin, Germany.
Aviv Regev, South San Francisco, Genentech, CA, USA.
Helene KretzmerMax Planck Institute for Molecular Genetics, Berlin, Germany.
Zachary D SmithBroad Institute of MIT and Harvard, Cambridge, MA, USA. smith@molgen.mpg.de.
Alexander MeissnerMax Planck Institute for Molecular Genetics, Berlin, Germany. meissner@molgen.mpg.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumors represent dynamically evolving populations of mutant cells, and many advances have been made in understanding the biology of their progression. However, there are key unresolved questions about the conditions that support a cell's initial transformation, which cannot be easily captured in patient populations and are instead modeled using transgenic cellular or animal systems.

resultsHere, we use extensive patient atlas data to define common features of the tumor DNA methylation landscape as they compare to healthy human cells and apply this benchmark to evaluate 21 engineered human and mouse models for their ability to reproduce these patterns. Notably, we find that genetically induced cellular transformation rarely recapitulates the widespread de novo methylation of Polycomb regulated promoter sequences as found in clinical samples, but can trigger global changes in DNA methylation levels that are consistent with extensive proliferation in vitro.

conclusionsOur results raise pertinent questions about the relationship between genetic and epigenetic aspects of tumorigenesis as well as provide an important molecular reference for evaluating existing and emerging tumor models.

Indexed as

Cell Transformation, NeoplasticDNA MethylationNeoplasmsAnimalsEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansMicePromoter Regions, GeneticCancerDisease modelsDNA methylationEpigeneticsGenetically engineered mouse models

Identifiers

PMID40676699
PMCPMC12273271

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.