Evidence map›Paper›PMID 31839337›Full record

ArticleGynecologic oncology2020

Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma.

Jeffrey D Krimmel-Morrison, Talayeh S Ghezelayagh, Shenyi Lian, Yuezheng Zhang, Jeanne Fredrickson, Daniela Nachmanson, Kathryn T Baker, Marc R Radke, Enna Hun, Barbara M Norquist and 3 more

Open access · greenAbstract read
In one paragraph

Article in Gynecologic oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 42% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
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  14. Early Detection of Ovarian Cancer.Cold Spring Harbor perspectives in medicine · 2023
    Review
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  16. Uterine lavage identifies cancer mutations and increasedCancer research communications · 2022
    Article
  17. Article
  18. 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 1 institution in 1 country.

Jeffrey D Krimmel-MorrisonDepartment of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Talayeh S GhezelayaghDepartment of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
Shenyi LianDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Yuezheng ZhangDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Jeanne FredricksonDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Daniela NachmansonDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Kathryn T BakerDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Marc R RadkeDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
Enna HunDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
Barbara M NorquistDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
Mary J EmondDepartment of Statistics, University of Washington, Seattle, WA 98195, USA.
Elizabeth M SwisherDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
Rosa Ana RisquesDepartment of Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address: rrisques@uw.edu.
University of Washington · US

Funding

Early Detection of Ovarian Cancer Using Uterine Lavage and Duplex SequencingR44CA221426 · NCI · TWINSTRAND BIOSCIENCES, INC. · PI SALK, JESSE J · 2017 to 2020
$2.3M
Mitochondrial biomarkers for early detection of cancer in ulcerative colitisR01CA181308 · NCI · UNIVERSITY OF WASHINGTON · PI RISQUES, ROSA ANA · 2014 to 2018
$1.4M
Evaluation of TP53 mutations in non-cancerous tissue as novel biomarkers of ovarian cancer risk.R21CA240885 · NCI · UNIVERSITY OF WASHINGTON · PI RISQUES, ROSA ANA · 2019 to 2020
$372k
NCI NIH HHS R01 CA181308NCI NIH HHS R21 CA240885NCI NIH HHS R44 CA221426
6 · The paper itself

Abstract

objectivePap tests hold promise as a molecular diagnostic for serous ovarian cancer, but previous studies reported limited sensitivity. Furthermore, the presence of somatic mutations in normal tissue is increasingly recognized as a challenge to the specificity of mutation-based cancer diagnostics. We applied an ultra-deep sequencing method with the goal of improving sensitivity and characterizing the landscape of low-frequency somatic TP53 mutations in Pap tests.

methodsWe used CRISPR-DS to deeply sequence (mean Duplex depth ~3000×) the TP53 gene in 30 Pap tests from 21 women without cancer and 9 women with serous ovarian carcinoma with known TP53 driver mutations. Mutations were annotated and compared to those in the TP53 cancer database.

resultsThe tumor-derived mutation was identified in 3 of 8 Pap tests from women with ovarian cancer and intact tubes. In addition, 221 low-frequency (≲0.001) exonic TP53 mutations were identified in Pap tests from women with ovarian cancer (94 mutations) and without ovarian cancer (127 mutations). Many of these mutations resembled TP53 mutations found in cancer: they impaired protein activity, were predicted to be pathogenic, and clustered in exons 5 to 8 and hotspot codons. Cancer-like mutations were identified in all women but at higher frequency in women with ovarian cancer.

conclusionsPap tests have low sensitivity for ovarian cancer detection and carry abundant low-frequency TP53 mutations. These mutations are more frequently pathogenic in women with ovarian cancer. Determining whether low-frequency TP53 mutations in normal gynecologic tissues are associated with an increased cancer risk warrants further study.

Indexed as

AdultAgedAged, 80 and overBiomarkers, TumorCohort StudiesCystadenocarcinoma, SerousDNADNA Mutational AnalysisFemaleHumansMiddle AgedMutationOvarian NeoplasmsPapanicolaou TestTumor Suppressor Protein p53Young AdultBiomarkers, TumorDNATP53 protein, humanTumor Suppressor Protein p53BiomarkerDeep sequencingEpithelial ovarian cancerPapanicolaou testTP53 gene

Identifiers

PMID31839337
PMCPMC7018621
OpenAlexW2996273379

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.