Evidence map›Paper›PMID 37318863›Full record

ArticleJCI insight2023

Circulating cell-free methylated DNA reveals tissue-specific, cellular damage from radiation treatment.

Megan E McNamara, Netanel Loyfer, Amber J Kiliti, Marcel O Schmidt, Sapir Shabi-Porat, Sidharth S Jain, Sarah Martinez Roth, A Patrick McDeed, Nesreen Shahrour, Elizabeth Ballew and 8 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.2field-weighted citation impact, top 13% 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.

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

15 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
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  4. Article
  5. Review
  6. Life science alliance · 2026
    Article
  7. Article
  8. Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  9. Review
  10. Article
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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 at 3 institutions in 2 countries.

Megan E McNamaraLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Netanel LoyferSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Amber J KilitiLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Marcel O SchmidtLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Sapir Shabi-PoratSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Sidharth S JainLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Sarah Martinez RothLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
A Patrick McDeedLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Nesreen ShahrourLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Elizabeth BallewMedstar Georgetown University Hospital, Washington DC, USA.
Yun-Tien LinLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Heng-Hong LiLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Anne Deslattes MaysScience and Technology Consulting, LCC, Farmington, Connecticut, USA.
Sonali RudraMedstar Georgetown University Hospital, Washington DC, USA.
Anna T RiegelLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Keith UngerMedstar Georgetown University Hospital, Washington DC, USA.
Tommy KaplanSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Anton WellsteinLombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.
Georgetown University · USHebrew University of Jerusalem · ILNational Institutes of Health · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Habtom W Ressom · 1990 to 2026
$71.5M
TRAINING GRANT IN TUMOR BIOLOGYT32CA009686 · NCI · GEORGETOWN UNIVERSITY · PI ANNA Tate RIEGEL, DAVID J ROBBINS · 1996 to 2026
$10.8M
(PQ #8) Biomarkers of efficacy and adverse events due to treatment with immune checkpoint inhibitorsR01CA231291 · NCI · GEORGETOWN UNIVERSITY · PI ATKINS, MICHAEL BENJAMIN, WELLSTEIN, ANTON · 2018 to 2022
$2.6M
Pharmacological Sciences Training Program (PSTP)T32GM142520 · NIGMS · GEORGETOWN UNIVERSITY · PI Patrick Alexander Forcelli, Anton Wellstein · 2022 to 2026
$1.3M
Decoding the Tissue of Origin of Cellular Damage from Cell-free DNA in Liquid BiopsiesF30CA250307 · NCI · GEORGETOWN UNIVERSITY · PI BAREFOOT, MEGAN EVELYN · 2021 to 2025
$176k
NCI NIH HHS F30 CA250307NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA231291NCI NIH HHS T32 CA009686NIGMS NIH HHS T32 GM142520
6 · The paper itself

Abstract

Radiation therapy is an effective cancer treatment, although damage to healthy tissues is common. Here we analyzed cell-free, methylated DNA released from dying cells into the circulation to evaluate radiation-induced cellular damage in different tissues. To map the circulating DNA fragments to human and mouse tissues, we established sequencing-based, cell-type-specific reference DNA methylation atlases. We found that cell-type-specific DNA blocks were mostly hypomethylated and located within signature genes of cellular identity. Cell-free DNA fragments were captured from serum samples by hybridization to CpG-rich DNA panels and mapped to the DNA methylation atlases. In a mouse model, thoracic radiation-induced tissue damage was reflected by dose-dependent increases in lung endothelial and cardiomyocyte methylated DNA in serum. The analysis of serum samples from patients with breast cancer undergoing radiation treatment revealed distinct dose-dependent and tissue-specific epithelial and endothelial responses to radiation across multiple organs. Strikingly, patients treated for right-sided breast cancers also showed increased hepatocyte and liver endothelial DNA in the circulation, indicating the impact on liver tissues. Thus, changes in cell-free methylated DNA can uncover cell-type-specific effects of radiation and provide a readout of the biologically effective radiation dose received by healthy tissues.

Indexed as

Cell-Free Nucleic AcidsDNA MethylationAnimalsDNAHepatocytesHumansLiverMiceCell-Free Nucleic AcidsDNABreast cancerEpigeneticsGeneticsOncologyRadiation therapy

Identifiers

PMID37318863
PMCPMC10443812
OpenAlexW4380785175

What OpenQuestion holds

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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.