CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes

Benetatos, Leonidas; Hatzimichael, Eleftheria; Dasoula, Aggeliki; Dranitsaris, George; Tsiara, Stavroula; Syrrou, Maria; Georgiou, Ioannis; Bourantas, Konstantinos L.

doi:10.1016/j.leukres.2009.06.019

Cited by 138 publications

(141 citation statements)

References 37 publications

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“…SNRPN hypermethylation was observed in 34.9% of myelodysplastic syndrome patients and in 50% of acute myeloid leukemia patients. 52 The methylation increases in gastric cancer tissues for BRINP1, EPHA5, and SEZ6L were associated with active H. pylori infection in gastric cancer patients and may represent regulatory events induced by H. pylori infection that persist and may be selected during progression to cancer.…”

Section: Discussionmentioning

confidence: 95%

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

et al. 2016

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Gastric cancers are the most frequent gastric malignancy and usually arise in the sequence of Helicobacter pylori-associated chronic gastritis. CpG methylation is a central mechanism of epigenetic gene regulation affecting cancer-related genes, and occurs early in gastric carcinogenesis. DNA samples from non-metaplastic gastric mucosa with variable levels of gastritis (non-metaplastic mucosa), intestinal metaplasia, or gastric cancer were screened with methylation arrays for CpG methylation of cancer-related genes and 30 gene targets were further characterized by high-definition bisulfite next-generation sequencing. In addition, data from The Cancer Genome Atlas were analyzed for correlation of methylation with gene expression. Overall, 13 genes had significantly increased CpG methylation in gastric cancer vs non-metaplastic mucosa (BRINP1, CDH11, CHFR, EPHA5, EPHA7, FGF2, FLI1, GALR1, HS3ST2, PDGFRA, SEZ6L, SGCE, and SNRPN). Further, most of these genes had corresponding reduced expression levels in gastric cancer compared with intestinal metaplasia, including novel hypermethylated genes in gastric cancer (FLI1, GALR1, SGCE, and SNRPN), suggesting that they may regulate neoplastic transformation from non-malignant intestinal metaplasia to cancer. Our data suggest a tumor-suppressor role for FLI1 in gastric cancer, consistent with recently reported data in breast cancer. For the genes with strongest methylation/expression correlation, namely FLI1, the expression was lowest in microsatellite-unstable tumors compared with other gastric cancer molecular subtypes. Importantly, reduced expression of hypermethylated BRINP1 and SGCE was significantly associated with favorable survival in gastric cancer. In summary, we report novel methylation gene targets that may have functional roles in discrete stages of gastric carcinogenesis and may serve as biomarkers for diagnosis and prognosis of gastric cancer.

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Section: Discussionmentioning

confidence: 95%

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

et al. 2016

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“…DNA damage in eukaryotes prompts NNAT, L3MBTL, p57, p73, PEG10, MEG3 and SNRPN imprinted loci have been reported in leukemia. [36][37][38][39][40][41][42][43] Most of these genes are regulating apoptosis and cell proliferation. For example, PEG10 interacts with SIAH1 that retards cell growth and mediates apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Systems properties of proteins encoded by imprinted genes

Sandhu¹

2010

Epigenetics

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“…More importantly, however, survival curves generated based on the median methylation of AML samples for each CpG sites show significant associations between increased survival and higher methylation at CG7 and CG9 ( Figure 12). Because CG7 and CG9 lie within the MEG3 promotor region, these results seemingly contradict a previous report which associated higher methylation of the MEG3 promotor with decreased survival in AML [100]. This is likely due to several possible factors centered around their method of methylation analysis for this region.…”

Section: Parameter Characteristic Valuecontrasting

confidence: 90%

“…Paradoxically, higher methylation at CpG sites within the MEG3 promotor region was significantly associated with increased survival by these patients. This conflicts with a previous report which found aberrant methylation to significantly associate with decreased AML patient survival, though this conflict is likely due to the method of methylation assessment [100]. However, given the growth-suppressing nature of MEG3 and its downstream miRNAs and their dependence on the MEG3 DMR and promotor region for their correct expression, a decrease in miRNA expression would be expected for the samples which have higher methylation at these CpG sites [6,7,98,114,115].…”

Section: Discussionmentioning

confidence: 58%

The DLK1-MEG3 locus in malignant cells of proposed primordial germ cell origins.

Sellers¹

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CpG methylation analysis of the MEG3 and SNRPN imprinted genes in acute myeloid leukemia and myelodysplastic syndromes

Cited by 138 publications

References 37 publications

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

Systems properties of proteins encoded by imprinted genes

The DLK1-MEG3 locus in malignant cells of proposed primordial germ cell origins.

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