ITPKA Gene Body Methylation Regulates Gene Expression and Serves as an Early Diagnostic Marker in Lung and Other Cancers.

INTRODUCTION:Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. METHODS:Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. RESULTS:Inositol-trisphosphate 3-kinase A gene a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITduanyu1529 contributes to tumorigenesis. We also demonstrated that ITduanyu1529 expression is regulated by epigenetic DNA methylation of ITduanyu1529 gene body through modulation of the binding of SP1 transcription factor to the ITduanyu1529 promoter. ITduanyu1529 gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITduanyu1529 gene body methylation first appeared at the in situ carcinoma stage and progressively increased after is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITduanyu1529 gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.

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