Evidence map›Paper›PMID 37020053›Full record

ArticleMolecular genetics and genomics : MGG2023

DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development.

Sara Ferreira Pires, Juliana Sobral de Barros, Silvia Souza da Costa, Marília de Oliveira Scliar, André Van Helvoort Lengert, Érica Boldrini, Sandra Regina Morini da Silva, Ljubica Tasic, Daniel Onofre Vidal, Ana Cristina Victorino Krepischi and 1 more

Abstract read
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In one paragraph

Article in Molecular genetics and genomics : MGG, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 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 4 institutions in 1 country.

Sara Ferreira PiresDepartment of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Juliana Sobral de BarrosDepartment of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Silvia Souza da CostaDepartment of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Marília de Oliveira ScliarDepartment of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
André Van Helvoort LengertMolecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, Brazil.
Érica BoldriniBarretos Children's Cancer Hospital, Barretos, Brazil.
Sandra Regina Morini da SilvaDepartment of Pathology, Barretos Cancer Hospital, Barretos, Brazil.
Ljubica TasicLaboratory of Biological Chemistry, Institute of Chemistry, University of Campinas, Campinas, Brazil.
Daniel Onofre VidalMolecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, Brazil.
Ana Cristina Victorino KrepischiDepartment of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Mariana MaschiettoBrazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil. marianamasc@gmail.com.ORCID http://orcid.org/0000-0003-2589-3186
Universidade de São Paulo · BRHospital de Câncer de Barretos · BRCentro Infantil Boldrini · BRUniversidade Estadual de Campinas (UNICAMP) · BR

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88887.508357/2020-00Fundação de Amparo à Pesquisa do Estado de São Paulo 14/10250-7Fundação de Amparo à Pesquisa do Estado de São Paulo 15/06281-7Fundação de Amparo à Pesquisa do Estado de São Paulo 18/06510-4Fundação de Amparo à Pesquisa do Estado de São Paulo 18/21047-9Fundação de Amparo à Pesquisa do Estado de São Paulo 18/24069-3
6 · The paper itself

Abstract

DNA methylation may be involved in the development of osteosarcomas. Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. As a highly studied epigenetic mechanism, we investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver alterations. Methylation and genomic data were obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response, and signal transduction. Both methylation and expression data were validated in independent groups of cases. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, and WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, and RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. Copy-number changes in DNMT3B (gain) and TET1 (loss), as well as overexpression of DNMT3B in osteosarcomas provide a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes.

Indexed as

Bone NeoplasmsMicroRNAsOsteosarcomaCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationEpigenesis, GeneticHumansMixed Function OxygenasesPromoter Regions, GeneticProto-Oncogene ProteinsTumor Suppressor ProteinsDLEC1 protein, humanDNA (Cytosine-5-)-MethyltransferasesMicroRNAsMIRN149 microRNA, humanMixed Function OxygenasesProto-Oncogene ProteinsTET1 protein, humanTumor Suppressor ProteinsCopy-number alterationsDNA methylationDNMTMutationsOsteosarcomaTET

Identifiers

PMID37020053
OpenAlexW4362604487

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.