Altered expression of imprinted genes in Wilms tumors

Hubertus, Jochen; Lacher, Martin; Rottenkolber, Marietta; Müller‐Höcker, Josef; Berger, Michael; Stehr, Maximilian; Schweinitz, Dietrich von; Kappler, Roland

doi:10.3892/or.2010.1113

Cited by 36 publications

(35 citation statements)

References 29 publications

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“…For example, on chromosome 11 (2.01–2.03 mega base (Mb)), the IGF2/H19 region was highlighted with 6 SNPs (Figure 2). This locus is a well-known imprinted region that is also linked to the Beckwith–Wiedemann syndrome and Wilms’ tumour (4,45–47). The H19 gene codes for a lncRNA of which expression is negatively correlated with the expression of the neighbouring gene insulin-like growth factor 2 ( IGF2 ).…”

Section: Discussionmentioning

confidence: 99%

SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data

Steyaert

Criekinge

Paepe

et al. 2014

Nucleic Acids Research

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Monoallelic gene expression is typically initiated early in the development of an organism. Dysregulation of monoallelic gene expression has already been linked to several non-Mendelian inherited genetic disorders. In humans, DNA-methylation is deemed to be an important regulator of monoallelic gene expression, but only few examples are known. One important reason is that current, cost-affordable truly genome-wide methods to assess DNA-methylation are based on sequencing post-enrichment. Here, we present a new methodology based on classical population genetic theory, i.e. the Hardy–Weinberg theorem, that combines methylomic data from MethylCap-seq with associated SNP profiles to identify monoallelically methylated loci. Applied on 334 MethylCap-seq samples of very diverse origin, this resulted in the identification of 80 genomic regions featured by monoallelic DNA-methylation. Of these 80 loci, 49 are located in genic regions of which 25 have already been linked to imprinting. Further analysis revealed statistically significant enrichment of these loci in promoter regions, further establishing the relevance and usefulness of the method. Additional validation was done using both 14 whole-genome bisulfite sequencing data sets and 16 mRNA-seq data sets. Importantly, the developed approach can be easily applied to other enrichment-based sequencing technologies, like the ChIP-seq-based identification of monoallelic histone modifications.

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Section: Discussionmentioning

confidence: 99%

SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data

Steyaert

Criekinge

Paepe

et al. 2014

Nucleic Acids Research

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“…Further, it was also observed to be associated with decreased H3K27me3 level at SNRPN DMR and H3K9me3 level at PEG10 DMR. This observed epigenetic dysregulation and upregulation of gene expression in molar villi might be contributing to enhanced cellular proliferation and invasion of molar tissue, as these genes are known to show similar aberrant changes in various tumors like Wilms and germ cell tumors5354. However, in JEG-3 cells minimal expression of these genes mediated by abnormally higher methylation at their DMRs, which suggests the possible role of aberrant hypermethylation at these DMRs in development of choriocarcinoma.…”

Section: Discussionmentioning

confidence: 88%

Epigenetic modifications at DMRs of placental genes are subjected to variations in normal gestation, pathological conditions and folate supplementation

Rahat

Mahajan

Bagga

et al. 2017

Sci Rep

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Invasive placentation and cancer development shares many similar molecular and epigenetic pathways. Paternally expressed, growth promoting genes (SNRPN, PEG10 and MEST) which are known to play crucial role in tumorogenesis, are not well studied during placentation. This study reports for the first time of the impact of gestational-age, pathological conditions and folic acid supplementation on dynamic nature of DNA and histone methylation present at their differentially methylated regions (DMRs). Here, we reported the association between low DNA methylation/H3K27me3 and higher expression of SNRPN, PEG10 and MEST in highly proliferating normal early gestational placenta. Molar and preeclamptic placental villi, exhibited aberrant changes in methylation levels at DMRs of these genes, leading to higher and lower expression of these genes, respectively, in reference to their respective control groups. Moreover, folate supplementation could induce gene specific changes in mRNA expression in placental cell lines. Further, MEST and SNRPN DMRs were observed to show the potential to act as novel fetal DNA markers in maternal plasma. Thus, variation in methylation levels at these DMRs regulate normal placentation and placental disorders. Additionally, the methylation at these DMRs might also be susceptible to folic acid supplementation and has the potential to be utilized in clinical diagnosis.

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“…Perturbations in imprinted gene expression occur in BeckwithWiedemann syndrome (BWS), Silver-Russell syndrome, intrauterine growth restriction, transient neonatal diabetes mellitus and congenital Wilms tumours. [62][63][64][65][66][67][68] The lack of imprinting in such diseases originates from a failure in establishing epigenetic marks in germ cells or maintaining them in the zygote or early embryo.…”

Section: Epigenetic Dysregulation In Prostate Cancermentioning

confidence: 99%

Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

Ribarska¹,

Bastian²,

Koch³

et al. 2012

Asian J Androl

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Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation, enhancer of zeste homologue 2 (EZH2) overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer. DNA methylation, EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes. Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes, expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2). A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms. Instead, selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes, which might function in the prostate to limit cell growth induced via the PI3K/Akt pathway, modulate androgen responses and regulate differentiation. Whereas dysregulation of IGF2 may constitute an early change in prostate carcinogenesis, inactivation of this imprinted gene network is rather associated with cancer progression.

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Altered expression of imprinted genes in Wilms tumors

Cited by 36 publications

References 29 publications

SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data

SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data

Epigenetic modifications at DMRs of placental genes are subjected to variations in normal gestation, pathological conditions and folate supplementation

Specific changes in the expression of imprinted genes in prostate cancer—implications for cancer progression and epigenetic regulation

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