Evidence map›Paper›PMID 31311767›Full record

ArticleDNA repair2019

Increased MTH1-specific 8-oxodGTPase activity is a hallmark of cancer in colon, lung and pancreatic tissue.

Lisa A McPherson, Clara I Troccoli, Debin Ji, Annie E Bowles, Makelle L Gardiner, Michael G Mohsen, Nagaraj S Nagathihalli, Dao M Nguyen, David J Robbins, Nipun B Merchant and 3 more

Open access · greenAbstract read
In one paragraph

Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023
    Article
  10. Chemical Tools for the Study of DNA Repair.Accounts of chemical research · 2022
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. 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

13 authors at 3 institutions in 1 country.

Lisa A McPhersonDivision of Oncology, Stanford University School of Medicine, Stanford, CA 94305-5151, United States.
Clara I TroccoliDepartment of Medicine/Division of Medical Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Debin JiDepartment of Chemistry, Stanford University, Stanford, CA 94305-4401, United States.
Annie E BowlesDivision of Oncology, Stanford University School of Medicine, Stanford, CA 94305-5151, United States.
Makelle L GardinerDivision of Oncology, Stanford University School of Medicine, Stanford, CA 94305-5151, United States.
Michael G MohsenDepartment of Chemistry, Stanford University, Stanford, CA 94305-4401, United States.
Nagaraj S NagathihalliSylvester Comprehensive Cancer Center, Miami, FL 33136, United States; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Dao M NguyenSylvester Comprehensive Cancer Center, Miami, FL 33136, United States; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
David J RobbinsSylvester Comprehensive Cancer Center, Miami, FL 33136, United States; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Nipun B MerchantSylvester Comprehensive Cancer Center, Miami, FL 33136, United States; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, United States.
Eric T KoolDepartment of Chemistry, Stanford University, Stanford, CA 94305-4401, United States.
Priyamvada RaiDepartment of Medicine/Division of Medical Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, United States; Sylvester Comprehensive Cancer Center, Miami, FL 33136, United States. Electronic address: PRai@med.miami.edu.
James M FordDivision of Oncology, Stanford University School of Medicine, Stanford, CA 94305-5151, United States. Electronic address: JMF@stanford.edu.
Stanford University · USUniversity of Miami · USSylvester Comprehensive Cancer Center · US

Funding

Measuring and Modulating Oxidative DNA Damage Surveillance PathwaysR01CA217809 · NCI · STANFORD UNIVERSITY · PI KOOL, ERIC T. · 2017 to 2024
$3.7M
MutT Homolog 1 as a Novel Mediator of RAS Oncogene-Induced Pro-Malignant PathwaysR01CA175086 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI RAI, PRIYAMVADA · 2013 to 2017
$1.6M
NCI NIH HHS R01 CA175086NCI NIH HHS R01 CA217809
6 · The paper itself

Abstract

Cellular homeostasis is dependent on a balance between DNA damage and DNA repair mechanisms. Cells are constantly assaulted by both exogenous and endogenous stimuli leading to high levels of reactive oxygen species (ROS) that cause oxidation of the nucleotide dGTP to 8-oxodGTP. If this base is incorporated into DNA and goes unrepaired, it can result in G > T transversions, leading to genomic DNA damage. MutT Homolog 1 (MTH1) is a nucleoside diphosphate X (Nudix) pyrophosphatase that can remove 8-oxodGTP from the nucleotide pool before it is incorporated into DNA by hydrolyzing it into 8-oxodGMP. MTH1 expression has been shown to be elevated in many cancer cells and is thought to be a survival mechanism by which a cancer cell can stave off the effects of high ROS that can result in cell senescence or death. It has recently become a target of interest in cancer because it is thought that inhibiting MTH1 can increase genotoxic damage and cytotoxicity. Determining the role of MTH1 in normal and cancer cells is confounded by an inability to reliably and directly measure its native enzymatic activity. We have used the chimeric ATP-releasing guanine-oxidized (ARGO) probe that combines 8-oxodGTP and ATP to measure MTH1 enzymatic activity in colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) along with patient-matched normal tissue. MTH1 8-oxodGTPase activity is significantly increased in tumors across all three tissue types, indicating that MTH1 is a marker of cancer. MTH1 activity measured by ARGO assay was compared to mRNA and protein expression measured by RT-qPCR and Western blot in the CRC tissue pairs, revealing a positive correlation between ARGO assay and Western blot, but little correlation with RT-qPCR in these samples. The adoption of the ARGO assay will help in establishing the level of MTH1 activity in model systems and in assessing the effects of MTH1 modulation in the treatment of cancer.

Indexed as

Cell Line, TumorColonic NeoplasmsDNA Repair EnzymesGene Knockout TechniquesHumansLung NeoplasmsNeoplasmsPancreatic NeoplasmsPhosphoric Monoester Hydrolases8-oxodGTPaseDNA Repair EnzymesPhosphoric Monoester Hydrolases8-oxodGTPCancerDNA repairGenetic instabilityMTH1Reactive oxygen species

Identifiers

PMID31311767
PMCPMC7390602
OpenAlexW2955594941

What OpenQuestion holds

Textmetadata
LicenceTDM
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.