Evidence map›Paper›PMID 23144859›Full record

ArticlePloS one2012

Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

Stine H Kresse, Halfdan Rydbeck, Magne Skårn, Heidi M Namløs, Ana H Barragan-Polania, Anne-Marie Cleton-Jansen, Massimo Serra, Knut Liestøl, Pancras C W Hogendoorn, Eivind Hovig and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
4.1field-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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

  1. Pooled it
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  16. Cells · 2022
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12 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

12 authors at 4 institutions in 3 countries.

Stine H KresseDepartment of Tumour Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Halfdan Rydbeck
Magne Skårn
Heidi M Namløs
Ana H Barragan-Polania
Anne-Marie Cleton-Jansen
Massimo Serra
Knut Liestøl
Pancras C W Hogendoorn
Eivind Hovig
Ola Myklebost
Leonardo A Meza-Zepeda
Oslo University Hospital · NOUniversity of Oslo · NOLeiden University Medical Center · NLIstituto Ortopedico Rizzoli · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOsteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL

findingsThe cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression) using a recurrence threshold of 6/19 (>30%) cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes.

conclusionsIntegrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between DNA copy number, DNA methylation and mRNA expression in osteosarcomas, contributing to better understanding of osteosarcoma biology.

Indexed as

Epigenesis, GeneticGene Expression Regulation, NeoplasticBone NeoplasmsCell Line, TumorCluster AnalysisDNA Copy Number VariationsDNA MethylationGene DosageGenes, NeoplasmGenome-Wide Association StudyHumansOligonucleotide Array Sequence AnalysisOsteosarcomaPolymorphism, Single NucleotideRNA, MessengerRNA, Messenger

Identifiers

PMID23144859
PMCPMC3492335
OpenAlexW2128188406

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.