Evidence map›Paper›PMID 42480518›Full record

ArticleMolecular cell2026

Disruption of microhomology-mediated end joining in Ewing sarcoma.

Shuhei Asada, Guangli Zhu, Jithma Prasad Abeykoon, Yutaro Tanaka, Huy Nguyen, Yuna Hirohashi, Divya R Iyer, Nicholas William Ashton, Sirisha Mukkavalli, Martha Velazquez and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. 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. Review
  2. Article
  3. Defective Microhomology-Mediated End-joining in SMARCB1-Deficient Tumors.bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Shuhei AsadaDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: shuhei_asada@dfci.harvard.edu.
Guangli ZhuDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Jithma Prasad AbeykoonDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Yutaro TanakaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Huy NguyenDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yuna HirohashiDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Divya R IyerDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nicholas William AshtonDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Sirisha MukkavalliDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Martha VelazquezDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Lige JiangDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Miles Del BussoDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Judith Jebastin ThangaiahDepartment of Pathology, Mayo Clinic, Rochester, MN, USA.
Steven I RobinsonDepartment of Oncology, Mayo Clinic, Rochester, MN, USA.
Kalindi ParmarDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Eliezer M Van AllenCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
Riaz GillaniDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Boston, MA, USA.
Geoffrey I ShapiroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alan D D'AndreaDivision of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: alan_dandrea@dfci.harvard.edu.

Funding

Tissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI LEIF W ELLISEN, NANCY U LIN · 2013 to 2026
$30.1M
Project 2: Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancerP50CA240243 · NCI · DANA-FARBER CANCER INST · PI CASTRO, CESAR M · 2020 to 2024
$11.5M
MOLECULAR PATHOGENESIS OF FANCONI ANEMIAR01HL052725 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI ALAN D. D'ANDREA · 1994 to 2026
$5.9M
Exploiting a Novel DNA Repair Defect in Ewing SarcomaR01CA296618 · NCI · DANA-FARBER CANCER INST · PI ALAN D. D'ANDREA · 2025 to 2026
$1.0M
NCI NIH HHS P50 CA168504NCI NIH HHS P50 CA240243NCI NIH HHS R01 CA296618NHLBI NIH HHS R01 HL052725
6 · The paper itself

Abstract

Ewing sarcoma (EwS) is a group of bone and soft-tissue cancers in children and young adults. Because EwS cells have pronounced sensitivity to radiation and chemotherapy-induced DNA damage, the oncoprotein EWS-FLI1 is likely to be involved in DNA repair. Here, we demonstrate that EWS-FLI1 causes a defect in microhomology-mediated end joining (MMEJ) repair. EWSR1 is a splicing factor that promotes the faithful splicing of the POLQ pre-mRNA, required for the expression of Polθ, a critical protein in the MMEJ pathway. Expression of EWS-FLI1 or depletion of EWSR1 causes increased POLQ exon 25 skipping, decreased Polθ expression, impaired MMEJ, and enhanced cellular sensitivity to inhibitors of the Fanconi anemia (FA), homologous recombination (HR), or non-homologous end joining (NHEJ) pathways, through the mechanism of synthetic lethality. Correction of POLQ exon 25 skipping restored Polθ expression and MMEJ activity in EwS. Inhibitors of the FA, HR, or NHEJ pathways may therefore provide a targeted therapy for EwS patients.

Indexed as

Bone NeoplasmsDNA End-Joining RepairOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSSarcoma, EwingCell Line, TumorDNA-Directed DNA PolymeraseDNA Polymerase thetaExonsGene Expression Regulation, NeoplasticHumansRNA-Binding ProteinsRNA SplicingDNA-Directed DNA PolymeraseDNA Polymerase thetaEWS-FLI fusion proteinEWSR1-FLI1 fusion protein, humanEWSR1 protein, humanOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSRNA-Binding Proteinsalternative end joiningCDK12DNA double-strand breaksDNA-PKcEwing sarcomaRBM39TMEJ

Identifiers

PMID42480518
PMCPMC13404124

What OpenQuestion holds

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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.