Evidence map›Paper›PMID 41792798›Full record

ArticleJournal of translational medicine2026

Novel driver gene MDC1 confers homologous recombination repair deficiency and genomic instability in chemoresistant relapsing ovarian cancer.

Michael Diaz, Nicole Gull, Pei-Chen Peng, Kruttika Dabke, Jessica Baker, Jennifer Sun, Juan Alvarado, Benjamin Bastin, Nimisha Mazumdar, Chintda Santiskulvong and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

16 authors.

Michael Diaz *Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nicole Gull *Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Pei-Chen PengCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Kruttika DabkeCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Jessica BakerCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Jennifer SunWomen's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Juan AlvaradoApplied Genomics, Computation and Translation Core, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Benjamin BastinApplied Genomics, Computation and Translation Core, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Nimisha MazumdarCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Chintda SantiskulvongApplied Genomics, Computation and Translation Core, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Andrew J LiWomen's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Beth Y KarlanDepartment of Obstetrics and Gynecology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90048, USA.
B J RimelWomen's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Sarah J ParkerProteomic and Metabolomics Core Facility at the Board of Governors Innovation Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Simon A GaytherCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Michelle R JonesCenter for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. michelle.jones@csmc.edu.ORCID 0000-0001-5466-3844

Funding

Identifying new drivers of ovarian cancer from the non-coding genome by converging germline risk variants and somatic mutationsR00CA256519 · NCI · CEDARS-SINAI MEDICAL CENTER · PI PENG, PEI-CHEN · 2023 to 2025
$745k
Identifying new drivers of ovarian cancer from the non-coding genome by converging germline risk variants and somatic mutationsK99CA256519 · NCI · CEDARS-SINAI MEDICAL CENTER · PI PENG, PEI-CHEN · 2021 to 2022
$400k
NCI NIH HHS K99 CA256519NCI NIH HHS R00 CA256519
6 · The paper itself

Abstract

backgroundNearly 80% of patients with High grade serous ovarian cancer (HGSOC) will experience recurrence within 5 years, but little is known about the mechanisms that drive this process.

methodsIn this study we used whole genome sequencing to assess SNV and SV burdens. These were in turn used to estimate clonal dynamics, genomic scarring, and establish mutational patterns.

resultsMutational burdens and clonal compositions are established early and are maintained throughout recurrence. Using both next generation and ultra long read sequencing to analyze single nucleotide and structural variants (SVs) we discovered that although tumors from the same patient remained relatively stable, homologous recombination repair proficient (HRP) and homologous recombination repair deficient (HRD) tumors presented with distinct clonal profiles. SV signature analysis revealed three distinct classes: tumors defined by DNA losses, DNA gains, and copy number neutral changes. Each class displayed structural variation affecting distinct regions of the genome. Ultra long read sequencing validated most of the SVs identified in short read sequencing and identified additional SVs. A novel candidate driver gene involved in DNA repair, MDC1, was significantly mutated in patients with HRP tumors.

conclusionsThe phenotype of high grade serous ovarian tumors, as defined by mutation and clonality profiles, is established early in disease development and remain largely unchanged through chemotherapy and recurrence. This, when considered with the significant inter-patient heterogeneity identified in HGSOC, demonstrates the need for personalized therapies based on tumor profiling. Loss of MDC1 increases invasive properties in cell lines and may drive HRD in a subset of patients.

Indexed as

Drug Resistance, NeoplasmGenomic InstabilityNeoplasm Recurrence, LocalNuclear ProteinsOvarian NeoplasmsRecombinational DNA RepairTrans-ActivatorsAdaptor Proteins, Signal TransducingCell Cycle ProteinsFemaleHumansMutationAdaptor Proteins, Signal TransducingCell Cycle ProteinsMDC1 protein, humanNuclear ProteinsTrans-ActivatorsChemoresistanceClonalityHigh grade serous ovarian cancerLong read sequencingRecurrenceStructural variants

Identifiers

PMID41792798
PMCPMC13081607

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.