English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  DNA mutations occur randomly and sporadically in growth-related genes, mostly on cytosines. Demethylation of cytosines may lead to genetic instability through spontaneous deamination. Aims were whole genome methylation and targeted mutation analysis of colorectal cancer (CRC)-related genes and mRNA expression analysis of  TP53  pathway genes.    Methods  Long interspersed nuclear element-1 (LINE-1) BS-PCR followed by pyrosequencing was performed for the estimation of global DNA metlyation levels along the colorectal normal-adenoma-carcinoma sequence. Methyl capture sequencing was done on 6 normal adjacent (NAT), 15 adenomatous (AD) and 9 CRC tissues. Overall quantitative methylation analysis, selection of top hyper/hypomethylated genes, methylation analysis on mutation regions and  TP53  pathway gene promoters were performed. Mutations of 12 CRC-related genes ( APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53 ) were evaluated. mRNA expression of  TP53  pathway genes was also analyzed.    Results  According to the LINE-1 methylation results, overall hypomethylation was observed along the normal-adenoma-carcinoma sequence. Within top50 differential methylated regions (DMRs), in AD-N comparison  TP73, NGFR, PDGFRA  genes were hypermethylated,  FMN1, SLC16A7  genes were hypomethylated. In CRC-N comparison  DKK2, SDC2, SOX1  genes showed hypermethylation, while  ERBB4, CREB5, CNTN1  genes were hypomethylated. In certain mutation hot spot regions significant DNA methylation alterations were detected. The  TP53  gene body was addressed by hypermethylation in adenomas.  APC ,  TP53  and  KRAS  mutations were found in 30, 15, 21% of adenomas, and in 29, 53, 29% of CRCs, respectively. mRNA expression changes were observed in several  TP53  pathway genes showing promoter methylation alterations.    Conclusions  DNA methylation with consecutive phenotypic effect can be observed in a high number of promoter and gene body regions through CRC development.    Electronic supplementary material  The online version of this article (10.1186/s12885-018-4609-x) contains supplementary material, which is available to authorized users.

Gene promoter and exon DNA methylation changes in colon cancer development – mRNA expression and tumor mutation alterations