Evidence map›Paper›PMID 31776133›Full record

ArticleCancer research2020

Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.

Gu Xiao, Devon Lundine, George K Annor, Jorge Canar, Viola Ellison, Alla Polotskaia, Patrick L Donabedian, Thomas Reiner, Galina F Khramtsova, Olufunmilayo I Olopade and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

12 authors at 5 institutions in 1 country.

Gu XiaoThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.
Devon LundineThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.ORCID 0000-0003-4845-3116
George K AnnorThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.
Jorge CanarThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.
Viola EllisonThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.
Alla PolotskaiaThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York.
Patrick L DonabedianDepartment of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Thomas ReinerDepartment of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Galina F KhramtsovaCenter for Clinical Cancer Genetics and Global Health and Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.
Olufunmilayo I OlopadeCenter for Clinical Cancer Genetics and Global Health and Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.ORCID 0000-0002-9936-1599
Alexander MazoDepartment of Biochemistry and Molecular Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
Jill BargonettiThe Department of Biological Sciences Hunter College, Belfer Building, City University of New York, New York, New York. bargonetti@genectr.hunter.cuny.edu.
Hunter College · USThe Graduate Center, CUNY · USMemorial Sloan Kettering Cancer Center · USUniversity of Chicago · USThomas Jefferson University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Radioiodinated Multifunctional PARP1 Imaging Probes for Diagnosis and TherapyR01CA204441 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI PILLARSETTY, NAGAVARAKISHORE · 2016 to 2020
$2.9M
EPA EP-W-17-011NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA204441
6 · The paper itself

Abstract

Over 80% of triple-negative breast cancers (TNBC) express mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis. In this study, we dissected the function and association between mtp53 and PARP using a number of different cell lines, patient-derived xenografts (PDX), tissue microarrays (TMA), and The Cancer Genome Atlas (TCGA) database. Endogenous mtp53 R273H and exogenously expressed R273H and R248W bound to nascent 5-ethynyl-2´-deoxyuridine-labeled replicating DNA. Increased mtp53 R273H enhanced the association of mtp53 and PARP on replicating DNA. Blocking poly-ADP-ribose gylcohydrolase also enhanced this association. Moreover, mtp53 R273H expression enhanced overall MCM2 levels, promoted cell proliferation, and improved the synergistic cytotoxicity of treatment with the alkylating agent temozolomide in combination with the PARP inhibitor (PARPi) talazoparib. Staining of p53 and PARP1 in breast cancer TMAs and comparison with the TCGA database indicated a higher double-positive signal in basal-like breast cancer than in luminal A or luminal B subtypes. Higher PARP1 protein levels and PAR proteins were detected in mtp53 R273H than in wild-type p53-expressing PDX samples. These results indicate that mtp53 R273H and PARP1 interact with replicating DNA and should be considered as dual biomarkers for identifying breast cancers that may respond to combination PARPi treatments. SIGNIFICANCE: p53 gain-of-function mutant 273H and PARP1 interact with replication forks and could serve as potential biomarkers for breast cancer sensitivity to PARP inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/3/394/F1.large.jpg.

Indexed as

DNA ReplicationGain of Function MutationAntineoplastic Agents, AlkylatingCell ProliferationDNA, NeoplasmFemaleHumansMinichromosome Maintenance Complex Component 2Poly (ADP-Ribose) Polymerase-1TemozolomideTriple Negative Breast NeoplasmsTumor Suppressor Protein p53Antineoplastic Agents, AlkylatingDNA, NeoplasmMCM2 protein, humanMinichromosome Maintenance Complex Component 2PARP1 protein, humanPoly (ADP-Ribose) Polymerase-1TemozolomideTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID31776133
PMCPMC7002183
OpenAlexW2991497484

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.