Evidence map›Paper›PMID 32000721›Full record

ArticleBMC cancer2020

Pattern of nucleotide variants of TP53 and their correlation with the expression of p53 and its downstream proteins in a Sri Lankan cohort of breast and colorectal cancer patients.

Vahinipriya Manoharan, Eric Hamilton Karunanayake, Kamani Hemamala Tennekoon, Sumadee De Silva, Ahamed Ilyas Ahamed Imthikab, Kanishka De Silva, Preethika Angunawela, Sameera Vishwakula, John Lunec

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

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

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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

9 authors at 3 institutions in 2 countries.

Vahinipriya ManoharanInstitute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 3, Sri Lanka.
Eric Hamilton KarunanayakeInstitute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 3, Sri Lanka.
Kamani Hemamala TennekoonInstitute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 3, Sri Lanka.
Sumadee De SilvaInstitute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 3, Sri Lanka. sum@ibmbb.cmb.ac.lk.ORCID http://orcid.org/0000-0002-0033-0849
Ahamed Ilyas Ahamed ImthikabInstitute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 3, Sri Lanka.
Kanishka De SilvaNational Cancer Institute, Maharagama, Sri Lanka.
Preethika AngunawelaDepartment of Pathology, Faculty of Medicine, University of Colombo, 25 Kynsey Road, Colombo 8, Sri Lanka.
Sameera VishwakulaDepartment of Statistics, Faculty of Science, University of Colombo, Colombo 3, Sri Lanka.
John LunecNorthern Institute for Cancer Research, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne, NE2 4AD, UK.
University of Colombo · LKNational Cancer Institute of Sri Lanka · LKNewcastle University · GB

Funding

Commonwealth Scholarship Commission of the UK LKCN-2015-100National Research Council, Sri Lanka 15-033
6 · The paper itself

Abstract

backgroundBreast cancer (BC) is known to be the most common malignancy in females whereas colorectal cancer (CRC) incidence also higher in both genders in Sri Lanka. TP53 is an important tumour suppressor gene and its somatic mutations are reported in approximately 27% of BC and 43% of CRC cases. Analysis of TP53 gene variants not only provides clues for the aetiology of the tumour formation, but also has an impact on treatment efficacy. The current study was conducted to investigate the pattern of TP53 variants in patients with BC and CRC from Sri Lanka.

methods30 patients with BC, 21 patients with CRC and an equal number of healthy controls were screened for mutational status of TP53 by polymerase chain reaction (PCR) followed by direct sequencing. In addition, a subset of these samples were analysed for the protein expression of p53 and comparison made with the mutational status of TP53. We also analysed the protein expression of p21 and MDM2 as potential indicators of p53 functional status and compared it with the protein expression of p53. Additionally, hotspot codons of the KRAS, BRAF and PIK3CA genes were also analysed in a subset of CRC patients.

resultsTwenty seven sequence variants, including several novel variants in the TP53 gene were found. Nine BC and seven CRC tumour samples carried pathogenic TP53 variants. Pathogenic point missense variants were associated with strong and diffuse positive staining for p53 by immunohistochemistry (IHC), whereas, wild type TP53 showed complete absence of positive IHC staining or rare positive cells, regardless of the type of cancer. There was no direct correlation between p21 or MDM2 expression and p53 expression in either BCs or CRCs. Four of the CRC patients had pathogenic hotspot variants in KRAS; three of them were on codon 12 and one was on codon 61.

conclusionThe prevalence of pathogenic somatic TP53 variants was 31 and 33.33% in the studied BC and CRC cohorts respectively. All of them were located in exons 5-8 and the pathogenic missense variants were associated with strong immuno-positive staining for p53.

Indexed as

Gene Expression Regulation, NeoplasticGenetic VariationAdultAgedAllelesAmino Acid SequenceBiomarkers, TumorBreast NeoplasmsCase-Control StudiesColorectal NeoplasmsDatabases, FactualFemaleGene ExpressionGenotypeHumansImmunohistochemistryBiomarkers, TumorTP53 protein, humanTumor Suppressor Protein p53Breast cancerColorectal cancerGenetic variationImmunohistochemistrySri LankaTP53

Identifiers

PMID32000721
PMCPMC6990524
OpenAlexW3013920629

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LicenceCC BY
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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.