Abstract 1425: Prognostic significance of promoter DNA methylation in patients with neuroblastoma

Author(s):  
Diana T. Lau ◽  
Luke B. Hesson ◽  
Murray D. Norris ◽  
Michelle Haber ◽  
Glenn M. Marshall ◽  
...  
2021 ◽  
Vol 10 ◽  
Author(s):  
Silvia Udali ◽  
Domenica De Santis ◽  
Filippo Mazzi ◽  
Sara Moruzzi ◽  
Andrea Ruzzenente ◽  
...  

BackgroundMechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.MethodsForty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. MT1G and MT1H gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.ResultsPatients with Cu serum concentration above the 80th percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60–18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P < 0.0001). MT1G and MT1H gene expression was significantly down-regulated in HCC as compared to N tissues (P < 0.05). MTs promoter was hypermethylated in 9 out of the 19 HCC tissues showing MTs down-regulation and methylation levels of three specific CpGs paralleled to an increased mortality rate among the 23 patients analyzed (P = 0.015).ConclusionsMT1G and MT1H act as potential tumor suppressor genes regulated through promoter DNA methylation and, together with serum Cu concentrations, be related to survival rate in HCC.


2012 ◽  
Vol 18 (20) ◽  
pp. 5690-5700 ◽  
Author(s):  
Diana T. Lau ◽  
Luke B. Hesson ◽  
Murray D. Norris ◽  
Glenn M. Marshall ◽  
Michelle Haber ◽  
...  

2012 ◽  
Vol 21 (11 Supplement) ◽  
pp. 68-68
Author(s):  
Diana T. Lau ◽  
Luke B. Hesson ◽  
Murray D. Norris ◽  
Glenn Marshall ◽  
Michelle Haber ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 622
Author(s):  
Omeima Abdullah ◽  
Ziad Omran ◽  
Salman Hosawi ◽  
Ali Hamiche ◽  
Christian Bronner ◽  
...  

Silencing of tumor suppressor genes (TSGs) through epigenetic mechanisms, mainly via abnormal promoter DNA methylation, is considered a main mechanism of tumorigenesis. The abnormal DNA methylation profiles are transmitted from the cancer mother cell to the daughter cells through the involvement of a macromolecular complex in which the ubiquitin-like containing plant homeodomain (PHD), and an interesting new gene (RING) finger domains 1 (UHRF1), play the role of conductor. Indeed, UHRF1 interacts with epigenetic writers, such as DNA methyltransferase 1 (DNMT1), histone methyltransferase G9a, erasers like histone deacetylase 1 (HDAC1), and functions as a hub protein. Thus, targeting UHRF1 and/or its partners is a promising strategy for epigenetic cancer therapy. The natural compound thymoquinone (TQ) exhibits anticancer activities by targeting several cellular signaling pathways, including those involving UHRF1. In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex. We also speculate on the possibility that TQ might specifically target UHRF1, with subsequent regulatory effects on other partners.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianfeng Xu ◽  
Jiejun Shi ◽  
Xiaodong Cui ◽  
Ya Cui ◽  
Jingyi Jessica Li ◽  
...  

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.


2010 ◽  
Vol 42 (12) ◽  
pp. 1093-1100 ◽  
Author(s):  
Julie Borgel ◽  
Sylvain Guibert ◽  
Yufeng Li ◽  
Hatsune Chiba ◽  
Dirk Schübeler ◽  
...  

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