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  Tumor suppressor gene (TSG) inactivation plays a crucial role in carcinogenesis.  FUS1, NPRL2/G21  and  RASSF1A  are TSGs from LUCA region at 3p21.3, a critical chromosomal region in lung cancer development. The aim of the study was to analyze and compare the expression levels of these 3 TSGs in NSCLC, as well as in macroscopically unchanged lung tissue surrounding the primary lesion, and to look for the possible epigenetic mechanism of TSG inactivation  via  gene promoter methylation.    Methods  Expression levels of 3 TSGs and 2 DNA methyltransferases, DNMT1 and DNMT3B, were assessed using real-time PCR method (qPCR) in 59 primary non-small cell lung tumors and the matched macroscopically unchanged lung tissue samples. Promoter methylation status of TSGs was analyzed using methylation-specific PCRs (MSP method) and Methylation Index (MI) value was calculated for each gene.    Results  The expression of all three TSGs were significantly different between NSCLC subtypes:  RASSF1A  and  FUS1  expression levels were significantly lower in squamous cell carcinoma (SCC), and NPRL2/G21 in adenocarcinoma (AC).  RASSF1A  showed significantly lower expression in tumors  vs  macroscopically unchanged lung tissues. Methylation frequency was 38–76 %, depending on the gene. The highest MI value was found for  RASSF1A  (52 %) and the lowest for  NPRL2/G21  (5 %). The simultaneous decreased expression and methylation of at least one  RASSF1A  allele was observed in 71 % tumor samples. Inverse correlation between gene expression and promoter methylation was found for  FUS1  (rs = −0.41) in SCC subtype. Expression levels of DNMTs were significantly increased in 75–92 % NSCLCs and were significantly higher in tumors than in normal lung tissue. However, no correlation between mRNA expression levels of DNMTs and DNA methylation status of the studied TSGs was found.    Conclusions  The results indicate the potential role of the studied TSGs in the differentiation of NSCLC histopathological subtypes. The significant differences in  RASSF1A  expression levels between NSCLC and macroscopically unchanged lung tissue highlight its possible diagnostic role in lung cancer  in situ  recognition. High percentage of lung tumor samples with simultaneous  RASSF1A  decreased expression and gene promoter methylation indicates its epigenetic silencing. However, DNMT overexpression doesn’t seem to be a critical determinate of its promoter hypermethylation.

respiratory research

Quantitative analysis of mRNA expression levels and DNA methylation profiles of three neighboring genes: FUS1, NPRL2/G21 and RASSF1A in non-small cell lung cancer patients