Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

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Genome-Wide DNA Methylation Analysis Shows Enrichment of Differential Methylation in “Open Seas” and Enhancers and Reveals Hypomethylation in DNMT3A Mutated Cytogenetically Normal AML (CN-AML)

Blood ◽

10.1182/blood.v120.21.653.653 ◽

2012 ◽

Vol 120 (21) ◽

pp. 653-653 ◽

Cited By ~ 2

Author(s):

Ying Qu ◽

Andreas Lennartsson ◽

Verena I. Gaidzik ◽

Stefan Deneberg ◽

Sofia Bengtzén ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cpg Island ◽

Cpg Islands ◽

Differential Methylation ◽

Methylation Analysis ◽

Cpg Sites ◽

Genome Wide ◽

Genomic Regions ◽

Methylation Patterns

Abstract Abstract 653 DNA methylation is involved in multiple biologic processes including normal cell differentiation and tumorigenesis. In AML, methylation patterns have been shown to differ significantly from normal hematopoietic cells. Most studies of DNA methylation in AML have previously focused on CpG islands within the promoter of genes, representing only a very small proportion of the DNA methylome. In this study, we performed genome-wide methylation analysis of 62 AML patients with CN-AML and CD34 positive cells from healthy controls by Illumina HumanMethylation450K Array covering 450.000 CpG sites in CpG islands as well as genomic regions far from CpG islands. Differentially methylated CpG sites (DMS) between CN-AML and normal hematopoietic cells were calculated and the most significant enrichment of DMS was found in regions more than 4kb from CpG Islands, in the so called open sea where hypomethylation was the dominant form of aberrant methylation. In contrast, CpG islands were not enriched for DMS and DMS in CpG islands were dominated by hypermethylation. DMS successively further away from CpG islands in CpG island shores (up to 2kb from CpG Island) and shelves (from 2kb to 4kb from Island) showed increasing degree of hypomethylation in AML cells. Among regions defined by their relation to gene structures, CpG dinucleotide located in theoretic enhancers were found to be the most enriched for DMS (Chi χ2<0.0001) with the majority of DMS showing decreased methylation compared to CD34 normal controls. To address the relation to gene expression, GEP (gene expression profiling) by microarray was carried out on 32 of the CN-AML patients. Totally, 339723 CpG sites covering 18879 genes were addressed on both platforms. CpG methylation in CpG islands showed the most pronounced anti-correlation (spearman ρ =-0.4145) with gene expression level, followed by CpG island shores (mean spearman rho for both sides' shore ρ=-0.2350). As transcription factors (TFs) have shown to be crucial for AML development, we especially studied differential methylation of an unbiased selection of 1638 TFs. The most enriched differential methylation between CN-AML and normal CD34 positive cells were found in TFs known to be involved in hematopoiesis and with Wilms tumor protein-1 (WT1), activator protein 1 (AP-1) and runt-related transcription factor 1 (RUNX1) being the most differentially methylated TFs. The differential methylation in WT 1 and RUNX1 was located in intragenic regions which were confirmed by pyro-sequencing. AML cases were characterized with respect to mutations in FLT3, NPM1, IDH1, IDH2 and DNMT3A. Correlation analysis between genome wide methylation patterns and mutational status showed statistically significant hypomethylation of CpG Island (p<0.0001) and to a lesser extent CpG island shores (p<0.001) and the presence of DNMT3A mutations. This links DNMT3A mutations for the first time to a hypomethylated phenotype. Further analyses correlating methylation patterns to other clinical data such as clinical outcome are ongoing. In conclusion, our study revealed that non-CpG island regions and in particular enhancers are the most aberrantly methylated genomic regions in AML and that WT 1 and RUNX1 are the most differentially methylated TFs. Furthermore, our data suggests a hypomethylated phenotype in DNMT3A mutated AML. Disclosures: No relevant conflicts of interest to declare.

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Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.40 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Jessilyn Dunn ◽

Haiwei Qiu ◽

Soyeon Kim ◽

Daudi Jjingo ◽

Ryan Hoffman ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

Methylation Status ◽

Western Diet ◽

Dependent Manner ◽

Gene Promoters ◽

Genome Wide ◽

Methylation Patterns ◽

Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

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Abstract P098: An Epigenome-wide Study of Obesity in African American Youth and Young Adults: Novel Findings, Replication in Neutrophils and Relationship With Gene Expression

Circulation ◽

10.1161/circ.135.suppl_1.p098 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Xiaoling Wang ◽

Yue Pan ◽

Haidong Zhu ◽

Guang Hao ◽

Xin Wang ◽

...

Keyword(s):

Gene Expression ◽

Older Adults ◽

Dna Methylation ◽

Young Adults ◽

Methylation Data ◽

Middle Aged ◽

Cpg Sites ◽

Genome Wide ◽

Obesity Status ◽

Youth And Young Adults

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.

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A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

PLoS Genetics ◽

10.1371/journal.pgen.1001316 ◽

2011 ◽

Vol 7 (2) ◽

pp. e1001316 ◽

Cited By ~ 142

Author(s):

Athma A. Pai ◽

Jordana T. Bell ◽

John C. Marioni ◽

Jonathan K. Pritchard ◽

Yoav Gilad

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Expression Levels ◽

Genome Wide ◽

A Genome ◽

Methylation Patterns ◽

Genome Wide Study ◽

Gene Expression Levels

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Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model

10.1101/2020.02.09.940965 ◽

2020 ◽

Author(s):

Thomas R. Ward ◽

Xianglong Zhang ◽

Louis C. Leung ◽

Bo Zhou ◽

Kristin Muench ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cell Model ◽

Copy Number Variants ◽

Induced Pluripotent Stem Cell ◽

Neuronal Model ◽

Autism Spectrum ◽

Genome Wide ◽

Induced Pluripotent ◽

Methylation Patterns

AbstractCopy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.

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Genome-wide DNA methylation analysis of pulmonary function in middle and old-aged Chinese monozygotic twins

Respiratory Research ◽

10.1186/s12931-021-01896-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Tong Wang ◽

Weijing Wang ◽

Weilong Li ◽

Haiping Duan ◽

Chunsheng Xu ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Pulmonary Function ◽

Monozygotic Twins ◽

Linear Mixed Effect Model ◽

Sequencing Analysis ◽

Mixed Effect ◽

Cpg Sites ◽

Genome Wide ◽

Genomic Regions

Abstract Background Previous studies have determined the epigenetic association between DNA methylation and pulmonary function among various ethnics, whereas this association is largely unknown in Chinese adults. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and pulmonary function among middle-aged Chinese monozygotic twins. Methods The monozygotic twin sample was drawn from the Qingdao Twin Registry. Pulmonary function was measured by three parameters including forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear mixed effect model was used to regress the methylation level of CpG sites on pulmonary function. After that, we applied Genomic Regions Enrichment of Annotations Tool (GREAT) to predict the genomic regions enrichment, and used comb-p python library to detect differentially methylated regions (DMRs). Gene expression analysis was conducted to validate the results of differentially methylated analyses. Results We identified 112 CpG sites with the level of P < 1 × 10–4 which were annotated to 40 genes. We identified 12 common enriched pathways of three pulmonary function parameters. We detected 39 DMRs located at 23 genes, of which PRDM1 was related to decreased pulmonary function, and MPL, LTB4R2, and EPHB3 were related to increased pulmonary function. The gene expression analyses validated DIP2C, ASB2, SLC6A5, and GAS6 related to decreased pulmonary function. Conclusion Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on pulmonary function. Several CpG sites, genes, biological pathways and DMRs are considered as possible crucial to pulmonary function.

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Significant associations between driver gene mutations and DNA methylation alterations across many cancer types

10.1101/145680 ◽

2017 ◽

Cited By ~ 1

Author(s):

Yun-Ching Chen ◽

Valer Gotea ◽

Gennady Margolin ◽

Laura Elnitski

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Thyroid Cancer ◽

Gene Mutations ◽

Driver Gene ◽

Driver Genes ◽

Cancer Subtypes ◽

Genome Wide ◽

Cancer Types ◽

Methylation Patterns

AbstractRecent evidence shows that mutations in several driver genes can cause aberrant methylation patterns, a hallmark of cancer. In light of these findings, we hypothesized that the landscapes of tumor genomes and epigenomes are tightly interconnected. We measured this relationship using principal component analyses and methylation-mutation associations applied at the nucleotide level and with respect to genome-wide trends. We found a few mutated driver genes were associated with genome-wide patterns of aberrant hypomethylation or CpG island hypermethylation in specific cancer types. We identified associations between 737 mutated driver genes and site-specific methylation changes. Moreover, using these mutation-methylation associations, we were able to distinguish between two uterine and two thyroid cancer subtypes. The driver gene mutation-associated methylation differences between the thyroid cancer subtypes were linked to differential gene expression in JAK-STAT signaling, NADPH oxidation, and other cancer-related pathways. These results establish that driver-gene mutations are associated with methylation alterations capable of shaping regulatory network functions. In addition, the methodology presented here can be used to subdivide tumors into more homogeneous subsets corresponding to their underlying molecular characteristics, which could improve treatment efficacy.Author summaryMutations that alter the function of driver genes by changing DNA nucleotides have been recognized as a key player in cancer progression. Recent evidence showed that DNA methylation, a molecular signature that is used for controlling gene expression and that consists of cytosine residues with attached methyl groups in the context of CG dinucleotides, is also highly dysregulated in cancer and contributes to carcinogenesis. However, whether those methylation alterations correspond to mutated driver genes in cancer remains unclear. In this study, we analyzed 4,302 tumors from 18 cancer types and demonstrated that driver gene mutations are inherently connected with the aberrant DNA methylation landscape in cancer. We showed that those driver gene-associated methylation patterns can classify heterogeneous tumors in a cancer type into homogeneous subtypes and have the potential to influence the genes that contribute to tumor growth. This finding could help us to better understand the fundamental connection between driver gene mutations and DNA methylation alterations in cancer and to further improve the cancer treatment.

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Genome-Wide DNA Methylation Analysis of Patients with Myelodysplastic Syndrome After Azacitidine Treatment.

Blood ◽

10.1182/blood.v114.22.600.600 ◽

2009 ◽

Vol 114 (22) ◽

pp. 600-600

Author(s):

Hyang-Min Byun ◽

Timothy Triche ◽

Hyeoung-Joon Kim ◽

Hee Nam Kim ◽

Yeo-Kyeoung Kim ◽

...

Keyword(s):

Dna Methylation ◽

Bone Marrow ◽

Who Classification ◽

Methylation Pattern ◽

Methylation Analysis ◽

Cpg Sites ◽

Genome Wide ◽

Methylation Patterns ◽

Dna Methylation Analysis ◽

Hypermethylated Genes

Abstract Abstract 600 Background: Azacitidine is hypothesized to exert its therapeutic effect in patients with myelodysplastic syndrome (MDS) through inhibition of DNA methylation. However to date no genomic DNA methylation pattern has been shown to predict response to azacitidine in patients with MDS, and no aberrantly silenced gene or group of genes has been shown to be reactivated by azacitidine that can be clearly linked to the beneficial clinical effect. We sought to identify the gene or group of aberrantly hypermethylated genes that are responsible for the therapeutic effect of azacitidine by retrospectively analyzing genome-wide DNA methylation profiles from bone marrow samples of a cohort of 113 patients with MDS treated with the DNA methylation inhibitor, azacitidine. Methods: Bone marrow aspirates were collected at time of diagnosis prior to treatment, after 4 cycles of azacitidine therapy and 8 cycles of therapy. DNA was isolated and bisulfite treated with the EZ-96 DNA Methylation-Gold Kit. DNA methylation analysis was performed on 27,578 CpG sites representing 14,475 genes (almost ¾ of known genes) using the Infinium Bead Array system for samples at the time of diagnosis, 4 and 8 cycles of therapy. Only 19,662 CpG sites were used for further analysis due to exclusion of CpG sites that were on the × chromosome, sites suspected of containing single nucleotide polymorphisms (SNP), and sites within DNA repeats. In total 91 samples were analyzed from 43 patients with MDS, which were selected to represent different disease classifications and responses to therapy, and bone marrow aspirates from 10 healthy control subjects without MDS. Results: Two-way hierarchical cluster analysis showed clear clustering of bone marrow samples taken from subjects without MDS. DNA methylation patterns from healthy controls clustered together, and pre and post azacitidine treatment samples from the same subject clustered together as well. Samples did not cluster by DNA methylation patterns for WHO classification, International Prognostic Scoring System (IPSS), cytogenetic abnormalities, or response to azacitidine. Supervised cluster analysis is ongoing. Global decreases in DNA methylation as measured by the average methylation for all 19,662 loci assayed did decrease with treatment and there was a trend for a larger decrease in DNA methylation in those patients who responded to azacitidine. Conclusion: In this pilot study of genome-wide DNA methylation analysis of MDS patients treated with azacitidine we find global decreases of DNA methylation. We were unable to identify a DNA methylation pattern or group of hypermethylated genes that would predict response to azacitidine. MDS samples did not cluster by WHO classification, IPSS or response to azacitidine. Larger translational studies are needed, but the possibility that DNA methylation decreases in patients treated with azacitidine serve as a pharmacological marker rather than a therapeutic target should also be considered Disclosures: Laird: Celgene: Consultancy. Yang:Celgene: Honoraria, Research Funding, Speakers Bureau.

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Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure

Hypertension ◽

10.1161/hypertensionaha.120.14973 ◽

2020 ◽

Vol 76 (1) ◽

pp. 195-205 ◽

Cited By ~ 1

Author(s):

Yisong Huang ◽

Miina Ollikainen ◽

Maheswary Muniandy ◽

Tao Zhang ◽

Jenny van Dongen ◽

...

Keyword(s):

Gene Expression ◽

Blood Pressure ◽

Dna Methylation ◽

Association Study ◽

Meta Analysis ◽

African Ancestry ◽

Cpg Sites ◽

Genome Wide ◽

Novel Association ◽

Peripheral Leukocytes

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P <1×10 −5 . In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated ( P <1×10 −7 ) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P <0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 ( TXNIP ) and cg00716257 ( JDP2 ) determined by environmental effects acting on both systolic BP and methylation levels.

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Genome-wide DNA Methylation Analysis in Pediatric Acute Myeloid Leukemia

Blood Advances ◽

10.1182/bloodadvances.2021005381 ◽

2022 ◽

Author(s):

Genki Yamato ◽

Tomoko Kawai ◽

Norio Shiba ◽

Junji Ikeda ◽

Yusuke Hara ◽

...

Keyword(s):

Dna Methylation ◽

Acute Myeloid Leukemia ◽

Adverse Events ◽

Myeloid Leukemia ◽

Genetic Alterations ◽

Binding Motif ◽

Cpg Sites ◽

Genome Wide ◽

Methylation Patterns ◽

Acute Myeloid

We investigated genome-wide DNA methylation patterns in 64 pediatric patients with acute myeloid leukemia (AML). Based on unsupervised clustering with 567 most variably methylated CpG sites, patients were categorized into four clusters associated with genetic alterations. Clusters 1 and 3 were characterized by the presence of known favorable prognostic factors, such as RUNX1-RUNX1T1 fusion and KMT2A rearrangement with low MECOM expression, and biallelic CEBPA mutations (all 8 patients), respectively. Clusters 2 and 4 comprised patients exhibiting molecular features associated with adverse outcomes, namely FLT3-ITD, KMT2A-PTD, and high PRDM16 expression. Depending on the methylation values of the 1243 CpG sites that were significantly different between FLT3-ITD positive and negative AML, patients were categorized into three clusters: A, B, and C. The STAT5-binding motif was most frequently found close to the 1,243 CpG sites. All eight patients with FLT3-ITD in Cluster A harbored high PRDM16 expression and experienced adverse events, whereas only one of seven patients with FLT3-ITD in the other clusters experienced adverse events. PRDM16 expression levels were also related to DNA methylation patterns, which were drastically changed at the cutoff value of PRDM16/ABL1 = 0.10. The assay for transposase-accessible chromatin sequencing of AMLs supported enhanced chromatin accessibilities around genomic regions, such as HOXB cluster genes, SCHIP1, and PRDM16, which were associated with DNA methylation changes in AMLs with FLT3-ITD and high PRDM16 expression. Our results suggest that DNA methylation levels at specific CpG sites are useful to support genetic alterations and gene expression patterns of patients with pediatric AML.

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