scholarly journals DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5974
Author(s):  
Aliki Ntzifa ◽  
Dora Londra ◽  
Theodoros Rampias ◽  
Athanasios Kotsakis ◽  
Vassilis Georgoulias ◽  
...  

Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (RASSF1A, RASSF10, APC, WIF-1, BRMS1, SLFN11, RARβ, SHISA3, and FOXA1) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (n = 80) and in paired CTCs (n = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (n = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (p = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism.

2021 ◽  
Vol 16 (3) ◽  
pp. S490
Author(s):  
D.M. Aguilar-Beltrán ◽  
A.G. Alcázar-Ramos ◽  
A.L. Vega-Rodríguez ◽  
D.G. García-Gutiérrez ◽  
A.D. Bertadillo-Jilote ◽  
...  

2021 ◽  
Vol 22 (8) ◽  
pp. 4247
Author(s):  
Andrea Martisova ◽  
Jitka Holcakova ◽  
Nasim Izadi ◽  
Ravery Sebuyoya ◽  
Roman Hrstka ◽  
...  

DNA methylation, i.e., addition of methyl group to 5′-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.


GigaScience ◽  
2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Katarzyna Murat ◽  
Björn Grüning ◽  
Paulina Wiktoria Poterlowicz ◽  
Gillian Westgate ◽  
Desmond J Tobin ◽  
...  

Abstract Background Infinium Human Methylation BeadChip is an array platform for complex evaluation of DNA methylation at an individual CpG locus in the human genome based on Illumina’s bead technology and is one of the most common techniques used in epigenome-wide association studies. Finding associations between epigenetic variation and phenotype is a significant challenge in biomedical research. The newest version, HumanMethylationEPIC, quantifies the DNA methylation level of 850,000 CpG sites, while the previous versions, HumanMethylation450 and HumanMethylation27, measured >450,000 and 27,000 loci, respectively. Although a number of bioinformatics tools have been developed to analyse this assay, they require some programming skills and experience in order to be usable. Results We have developed a pipeline for the Galaxy platform for those without experience aimed at DNA methylation analysis using the Infinium Human Methylation BeadChip. Our tool is integrated into Galaxy (http://galaxyproject.org), a web-based platform. This allows users to analyse data from the Infinium Human Methylation BeadChip in the easiest possible way. Conclusions The pipeline provides a group of integrated analytical methods wrapped into an easy-to-use interface. Our tool is available from the Galaxy ToolShed, GitHub repository, and also as a Docker image. The aim of this project is to make Infinium Human Methylation BeadChip analysis more flexible and accessible to everyone.


BioTechniques ◽  
2006 ◽  
Vol 40 (6) ◽  
pp. 721-726 ◽  
Author(s):  
Jörg Tost ◽  
Hafida El abdalaoui ◽  
Ivo Glynne Gut

2006 ◽  
Vol 19 (8) ◽  
pp. 1083-1090 ◽  
Author(s):  
Shuji Ogino ◽  
Mohan Brahmandam ◽  
Takako Kawasaki ◽  
Gregory J Kirkner ◽  
Massimo Loda ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document