scholarly journals Comprehensive methylation analysis of imprinting-associated differentially methylated regions in colorectal cancer

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Hidenori Hidaka ◽  
Ken Higashimoto ◽  
Saori Aoki ◽  
Hiroyuki Mishima ◽  
Chisa Hayashida ◽  
...  
2021 ◽  
Vol 43 (3) ◽  
pp. 1419-1435
Author(s):  
Walter Pulverer ◽  
Kristi Kruusmaa ◽  
Silvia Schönthaler ◽  
Jasmin Huber ◽  
Marko Bitenc ◽  
...  

Early diagnosis of colorectal cancer (CRC) is of high importance as prognosis depends on tumour stage at the time of diagnosis. Detection of tumour-specific DNA methylation marks in cfDNA has several advantages over other approaches and has great potential for solving diagnostic needs. We report here the identification of DNA methylation biomarkers for CRC and give insights in our methylation-sensitive restriction enzyme coupled qPCR (MSRE-qPCR) system. Targeted microarrays were used to investigate the DNA methylation status of 360 cancer-associated genes. Validation was done by qPCR-based approaches. A focus was on investigating marker performance in cfDNA from 88 patients (44 CRC, 44 controls). Finally, the workflow was scaled-up to perform 180plex analysis on 110 cfDNA samples, to identify a DNA methylation signature for advanced colonic adenomas (AA). A DNA methylation signature (n = 44) was deduced from microarray experiments and confirmed by quantitative methylation-specific PCR (qMSP) and by MSRE-qPCR, providing for six genes’ single areas under the curve (AUC) values of >0.85 (WT1, PENK, SPARC, GDNF, TMEFF2, DCC). A subset of the signatures can be used for patient stratification and therapy monitoring for progressed CRC with liver metastasis using cfDNA. Furthermore, we identified a 35-plex classifier for the identification of AAs with an AUC of 0.80.


Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 747-755
Author(s):  
Veronika Suni ◽  
Fatemeh Seyednasrollah ◽  
Bishwa Ghimire ◽  
Sini Junttila ◽  
Asta Laiho ◽  
...  

Aim: DNA methylation is a key epigenetic mechanism regulating gene expression. Identifying differentially methylated regions is integral to DNA methylation analysis and there is a need for robust tools reliably detecting regions with significant differences in their methylation status. Materials & methods: We present here a reproducibility-optimized test statistic (ROTS) for detection of differential DNA methylation from high-throughput sequencing or array-based data. Results: Using both simulated and real data, we demonstrate the ability of ROTS to identify differential methylation between sample groups. Conclusion: Compared with state-of-the-art methods, ROTS shows competitive sensitivity and specificity in detecting consistently differentially methylated regions.


2019 ◽  
Vol 8 (5) ◽  
pp. 2133-2145 ◽  
Author(s):  
Joe Ibrahim ◽  
Ken Op de Beeck ◽  
Erik Fransen ◽  
Lieselot Croes ◽  
Matthias Beyens ◽  
...  

2019 ◽  
Vol 68 (3) ◽  
pp. 782-785
Author(s):  
Carlos Rogelio Alvizo-Rodriguez ◽  
Maria de la Luz Ayala-Madrigal ◽  
Jesus Arturo Hernandez-Sandoval ◽  
Helen Haydee Fernanda Ramirez-Plascencia ◽  
Christian Octavio Gonzalez-Villaseñor ◽  
...  

The present study aimed to analyze the methylation pattern of the MIR200 family in the colorectal tissues and peripheral blood of colorectal cancer (CRC) patients. Previous informed consent, 102 samples of colorectal tissues (tumor and adjacent normal tissues) and 40 peripheral blood samples were collected from CRC patients. Additionally, we included a reference group of 40 blood samples. DNA extraction was done for colorectal tissues and peripheral blood. For methylation-specific PCR, we used bisulfite-treated DNA and controls for methylated and unmethylated DNA were included to each assay. PCR fragments were separated by 6% polyacrylamide gel electrophoresis. Methylation-positive and methylation-negative results were confirmed by bisulfite genomic sequencing technique. We analyzed 102 colorectal tissues and 40 blood samples from 51 CRC patients. MIR200B/MIR200A/MIR429 methylation analysis discloses no differences among tissues (p>0.05). However, MIR200C/MIR141 methylation showed differences between colorectal tissues and peripheral blood of CRC patients (p<0.0001) and mainly methylated alleles were observed in peripheral blood. These findings suggest a tissue-specific methylation pattern for the MIR200C/MIR141 promoter.


2017 ◽  
Vol 15 (4) ◽  
pp. 495 ◽  
Author(s):  
Soo-Kyung Park ◽  
Hae Lim Baek ◽  
Junghee Yu ◽  
Ji Yeon Kim ◽  
Hyo-Joon Yang ◽  
...  

2018 ◽  
Vol 43 (1) ◽  
pp. 176-188 ◽  
Author(s):  
Ana B. Crujeiras ◽  
Sonsoles Morcillo ◽  
Angel Diaz-Lagares ◽  
Juan Sandoval ◽  
Daniel Castellano-Castillo ◽  
...  

Genomics ◽  
2021 ◽  
Author(s):  
Lei Zhang ◽  
Dapeng Li ◽  
Fenqi Du ◽  
Hao Huang ◽  
Chao Yuan ◽  
...  

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Sander Bach ◽  
Nina R Sluiter ◽  
Jamie J Beagan ◽  
Joost M Mekke ◽  
Johannes C F Ket ◽  
...  

AbstractBackgroundLiquid biopsies could improve diagnosis, prognostication, and monitoring of colorectal cancer (CRC). Mutation, chromosomal copy number alteration, and methylation analysis in circulating tumor DNA (ctDNA) from plasma or serum has gained great interest. However, the literature is inconsistent on preferred candidate markers, hampering a clear direction for further studies and clinical translation. This review assessed the potential of ctDNA analysis for clinical utility.MethodsA systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines was conducted up to December 3, 2018, followed by methodological quality assessment. Primary endpoints were accuracy for detection, prognostication, and monitoring.ResultsEighty-four studies were included. For CRC detection, sensitivity was 75% using ctDNA mutation analysis and up to 96% using copy number analysis. Septin 9 (SEPT9) hypermethylation analysis showed sensitivities of 100% and specificities of 97%. Regarding prognostication, ctDNA KRAS mutations were associated with oncological outcome and could predict response to anti–epidermal growth factor receptor therapy. For monitoring, sequential ctDNA KRAS mutation analysis showed promise for detection of relapses or therapy resistance.ConclusionsThis comprehensive overview of ctDNA candidate markers demonstrates SEPT9 methylation analysis to be promising for CRC detection, and KRAS mutation analysis could assist in prognostication and monitoring. Prospective evaluation of marker panels in clinical decision making should bring ctDNA analysis into practice.


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