Evidence map›Paper›PMID 12578990›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2003

Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations.

Elizabeth Mambo, Xiangqun Gao, Yoram Cohen, Zhongmin Guo, Paul Talalay, David Sidransky

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.

  1. Pooled it
  2. Mitochondrial microsatellite instability in patients with metastatic colorectal cancer.Virchows Archiv : an international journal of pathology · 2015
    Pooled it
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  18. Molecular Oncology of Gall Bladder Cancer.Indian journal of surgical oncology · 2021
    Review
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9 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Elizabeth MamboDepartment of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Xiangqun Gao
Yoram Cohen
Zhongmin Guo
Paul Talalay
David Sidransky
Johns Hopkins University · US

Funding

INTEGRATED DEVELOPMENT OF NOVEL MOLECULAR MARKERSU01CA084986 · NCI · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 1999 to 2014
$33.8M
NCI NIH HHS 5 U01 CA84986-04NCI NIH HHS U01 CA084986
6 · The paper itself

Abstract

mtDNA mutations occur in a wide variety of degenerative diseases and cancer. mtDNA seems to be more susceptible to DNA damage and consequently sustains higher rates of mutation than does nuclear DNA (nDNA). Many of the somatic mtDNA mutations in human cancers are located in the displacement loop (D-loop) and in particular in a polycytidine stretch (C-tract) termed D310. The D310 region exhibits polymorphic length variation among individuals and has been described as a "hot spot" for somatic mutations in many cancer types. We used real-time quantitative PCR to analyze mtDNA integrity, damage repair, and induced mutations after exposure of human adult retinal pigment epithelial (ARPE)-19 cells to 4-nitroquinoline 1-oxide, a UV-mimetic and adduct-forming carcinogen, and tert-butyl hydroperoxide, an oxidant. The mtDNA-damage profile depended on the region. Thus, the tRNA coding for glycine (tRNA(G)) was the least affected region, whereas the D-loop, and especially its D310 region, were most sensitive to damage. The time course of repair of mutations of the D-loop and especially the D310 region after exposure to DNA-damaging agents was delayed when compared with other regions and gave rise to common D310 C-tract frame-shift mutations. The induced mutations in the D310 region were predominantly homoplasmic only 7 days after exposure to damage. Our results establish that the D-loop (especially its D310 region) is highly susceptible to mutations because of its vulnerability to DNA damage and inefficient repair mechanisms. Our findings may explain the high frequency of homoplasmic D310 somatic mutations in many tumor types.

Indexed as

DNA DamageEvolution, MolecularMutationOxidative StressBase SequenceCloning, MolecularDNA, MitochondrialDNA PrimersHumansMutagensPolymerase Chain ReactionDNA, MitochondrialDNA PrimersMutagens

Identifiers

PMID12578990
PMCPMC149920
OpenAlexW2040455470

What OpenQuestion holds

Textmetadata
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.