Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non-small cell lung cancer and surrounding tissues.
We used methylation-sensitive high resolution melting analysis to assess methylation of CpG islands within the promoters of the TIMP4, GATA4, SOX18, and EGFL7 genes in samples of non-small cell lung cancer and surrounding apparently normal tissue and noncancerous lung tissues. We found that the promoter methylation was heterogeneous in both tumor and surrounding normal tissue. This is in contrast to healthy lung tissue, where the promoters were normally either non- or hypomethylated, and the heterogeneity of methylation was low. An increased heterogeneity of methylation in the normal tissues surrounding the tumor may suggest an early start of epigenetic processes preceding genetic and morphologic changes and can be used as a biomarker of early cancerization events. This analysis is an easy and sensitive tool for studying epigenetic heterogeneity and could be used in clinical practice.
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow. tatazhik@ibch.ru
Tatyana
T
Azhikina
Alena
A
Kozlova
Timofey
T
Skvortsov
Eugene
E
Sverdlov
D002135:Calcium-Binding Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors / Q000235:genetics*; D044127:Epigenesis, Genetic; D050991:GATA4 Transcription Factor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055760:SOXF Transcription Factors / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; D016228:Endothelial Growth Factors; D050991:GATA4 Transcription Factor; D005819:Genetic Markers; D055760:SOXF Transcription Factors; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C527877:EGFL7 protein, human; C484170:GATA4 protein, human; C095473:SOX18 protein, human