Evidence map›Paper›PMID 24093668›Full record

ArticleBMC cancer2013

Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors.

Jovana Klajic, Thomas Fleischer, Emelyne Dejeux, Hege Edvardsen, Fredrik Warnberg, Ida Bukholm, Per Eystein Lønning, Hiroko Solvang, Anne-Lise Børresen-Dale, Jörg Tost and 1 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 9 pooled it
4.5field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 9 syntheses or guidelines pooled it, 74 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

11 authors at 6 institutions in 3 countries.

Jovana KlajicDepartment of Clinical Molecular Biology and Laboratory Science (EpiGen), Akershus University hospital, Division of Medicine, 1476 Lørenskog, Norway. v.n.kristensen@medisin.uio.no.
Thomas Fleischer
Emelyne Dejeux
Hege Edvardsen
Fredrik Warnberg
Ida Bukholm
Per Eystein Lønning
Hiroko Solvang
Anne-Lise Børresen-Dale
Jörg Tost
Vessela N Kristensen
Norwegian Cancer Society · NOAkershus University Hospital · NOCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRUniversity of Bergen · NOUniversity of Oslo · NOUppsala University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression.

methodsQuantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV.

resultsSignificant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival.

conclusionsIn the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above.

Indexed as

DNA MethylationBreast NeoplasmsCpG IslandsEpigenesis, GeneticErb-b2 Receptor Tyrosine KinasesFemaleGene Expression ProfilingHumansMutationNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPrognosisReceptors, EstrogenReceptors, ProgesteroneRisk FactorsErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenReceptors, ProgesteroneTumor Suppressor Protein p53

Identifiers

PMID24093668
PMCPMC3819713
OpenAlexW2096996041

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.