Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma

Bethge, Nicole; Honne, Hilde; Andresen, Kim; Trøen, Gunhild; Eknæs, Mette; Liestøl, Knut; Holte, Harald; Delabie, Jan; Smeland, Erlend B.; Lind, Guro Elisabeth

doi:10.4161/epi.27554

Cited by 32 publications

(29 citation statements)

References 55 publications

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“…Previous studies have shown that expression of SNCA is regulated by hypermethylation of the CpG island in its promoter region in various human cancers . Demethylation drug treatment in MB cells showed reversed expression of this gene, suggesting that the silenced expression of SNCA might be due to epigenetic regulation, including DNA hypermethylation (Figure A).…”

Section: Resultsmentioning

confidence: 83%

SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis

Jiang

et al. 2018

Cancer Science

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Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. One hundred and six MB samples were examined. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA,FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and α‐synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA revealed the ability of this gene to inhibit tumor invasion and induce apoptosis. Methylation‐specific PCR and pyrosequencing analysis showed that epigenetic mechanisms, rather than DNA hypermethylation, might play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.

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Section: Resultsmentioning

confidence: 83%

SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis

Jiang

et al. 2018

Cancer Science

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“…3b). It is noteworthy that the CNRIP1 gene, which encodes a protein that interacts with the C-terminal tail of cannabinoid receptor 1, has been found to be frequently methylated in hematological cancer types (Bethge et al 2014). 3f; P = 0.78, Student's t-test).…”

Section: Validation Of Gene Methylation/hydroxymethylation By Qpcrmentioning

confidence: 99%

Inhibition of DNA methyltransferases regulates cocaine self‐administration by rats: a genome‐wide DNA methylation study

Fonteneau

Filliol

Anglard

et al. 2016

Genes Brain and Behavior

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DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine. To obtain some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated with or without dAZA. The study identified nearly 189 000 differentially methylated regions (DMRs), about half of them were located inside gene bodies, while only 9% of DMRs were found in the promoter regions of genes. About 99% of methylation changes occurred outside CpG islands. Gene expression studies confirmed the inverse correlation usually observed between increased methylation and transcriptional activation when methylation occurs in the gene promoter. This inverse correlation was not observed when methylation took place inside gene bodies. Using the literature-based Ingenuity Pathway Analysis, we explored how the differentially methylated genes were related. The analysis showed that increase in cocaine intake by rats in response to DNA methyltransferase inhibitors underlies plasticity mechanisms which mainly concern axonal growth and synaptogenesis as well as spine remodeling. Together with the Akt/PI3K pathway, the Rho-GTPase family was found to be involved in the plasticity underlying the effect of dAZA on the observed behavioral changes.

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“…59665; Qiagen GmbH) as a negative control, unconverted human genomic DNA from healthy human blood samples, which was not amplified, and a no template control, including the entire ingredients of the reaction except the template DNA. The standard curve was plotted using the Cq value (13,14,18,19,34,37) of the methylated human bisulfite-converted DNA at various concentrations vs. the log value of input DNA concentration. An acceptable MethyLight PCR result was obtained, and is demonstrated by the PCR efficiency (96-102%), correct slope value (-3.65 --3.2) and R 2 =0.9985.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, it was reported that no significant difference was identified in the methylation status of these genes with clinicopathological characteristics of patients with CRC (17). Bethge et al (19) assessed CNRIP1, FBN1, INA, MAL, SNCA and SPG20 genes in 97 cancer cell lines, demonstrating that SNCA and SPG20 were methylated in 97 and 92% of the tumor samples, respectively. In the present study, it was demonstrated that SPG20 methylation exhibited a significantly higher sensitivity (81.1%) compared with the CEA tumor marker (48.6%).…”

Section: Hypermethylation Status In Plasma --------------------------mentioning

confidence: 99%

“…There are numerous reports of methylation biomarkers tested in fecal and plasma samples (12)(13)(14)(15). Previous epigenomic studies have revealed that a number of genes, including spastic paraplegia 20 (SPG20), can potentially be silenced in patients with CRC due to DNA hypermethylation within promoter regions (16)(17)(18)(19). This has prompted the opportunity to implement a reliable, inexpensive and simple approach for CRC detection (16,17).…”

Section: Introductionmentioning

confidence: 99%

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Detection of SPG20 gene promoter-methylated DNA, as a novel epigenetic biomarker, in plasma for colorectal cancer diagnosis using the MethyLight method

et al. 2017

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Abstract. Aberrant promoter methylation of genes is a common epigenetic alteration in colorectal cancer (CRC). In the present study, spastic paraplegia 20 (SPG20) promoter-methylated DNA, as a potential diagnostic biomarker, was investigated in plasma and tumor tissue samples from patients with CRC. To the best of our knowledge, the quantification of SPG20 promoter-methylated DNA in plasma samples remains unreported. SPG20 promoter methylation was investigated in 32 paired tumor and healthy adjacent tissues, 37 plasma samples from patients with CRC, and in 37 plasma samples from a healthy control group, using the MethyLight method. The percentage of methylated reference (PMR) values was determined for each sample, and the sensitivity and specificity of this unique biomarker were evaluated. PMR values were significantly higher in plasma samples from patients with CRC compared with in those from the control group (P<0.05). Plasma specimens from patients and healthy controls exhibited median PMR values of 7.7 (95% CI, 4.15-15.28) and 0.59 (95% CI, 0.14-1.12), respectively. Notably, the median PMR values were identified as 42.39 (95% CI, 27.69-72.26) and 3.61 (95% CI, 1.07-5.29) in tumor and adjacent healthy tissues, respectively. Using receiver-operating characteristics curve analysis, the area under curve (AUC) was demonstrated to be 0.984 for plasma samples, exhibiting a sensitivity of 81.1% and a specificity of 96.9%. Furthermore, the AUC was 0.996 for tissue samples, revealing a sensitivity of 93.8% and specificity of 99.96%.Results from the present study indicate that the identification of SPG20 promoter-methylated DNA in plasma is a potential diagnostic biomarker for the detection of CRC. Furthermore, the results demonstrate a satisfactory sensitivity and specificity, indicating the importance of SPG20 methylation as a novel noninvasive biomarker. IntroductionColorectal cancer (CRC) is one of the most common malignancies worldwide, accounting for an estimated 1.3 million new cases and >500,000 mortalities/year (1). CRC is the fourth leading cause of cancer-associated mortality worldwide, with a rapidly increasing incidence rate in the worldwide (2,3). In the Asian population, the annual prevalence rate of CRC has steadily increased over the past two decades (4). The Ministry of Health and Medical Education in Iran states that cancer is the third most common cause of mortality in Iran (5). Currently, the gold standard method for CRC detection is internal imaging of the colon with colonoscopy followed by a biopsy examination; however, it remains an invasive procedure with possible serious complications and limitations (6). Cancer is a multistep process resulting from a gradual accumulation of genetic and epigenetic changes to the genome (7). The methylation of 5'-C-phosphate-G-3' (CpG) islands has been suggested to be associated with gene silencing, serving an important role in cancer development (8,9). The aberrant promoter methylation of genes is a primary occurrence in the process of CRC carcinogenesis, whic...

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Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma

Cited by 32 publications

References 55 publications

SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis

SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis

Inhibition of DNA methyltransferases regulates cocaine self‐administration by rats: a genome‐wide DNA methylation study

Detection of SPG20 gene promoter-methylated DNA, as a novel epigenetic biomarker, in plasma for colorectal cancer diagnosis using the MethyLight method

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