Genome‐wide investigation of intragenic DNA methylation identifies ZMIZ1 gene as a prognostic marker in glioblastoma and multiple cancer types
| Autor: | Taeyoung Hwang, Peter C. Burger, Victor E. Velculescu, Zineb Belcaid, Russell Maxwell, Leslie Cope, Drew M. Pardoll, Alfred P. See, Chul-Kee Park, Gary L. Gallia, Mihoko Kai, Yuan Rui, Michael Lim, Henry Brem, Chetan Bettegowda, Patrick K. Ha, Joshua Casaos, Yuanxuan Xia, Jordan J. Green, Jillian Phallen, Dimitrios Mathios, Kerrie L. McDonald |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Transcription Genetic Mice Nude Biology Genome Epigenesis Genetic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Cell Line Tumor Molecular marker Biomarkers Tumor medicine Animals Epigenetics Promoter Regions Genetic Gene Brain Neoplasms Cancer Promoter Methylation DNA Methylation Prognosis medicine.disease Gene Expression Regulation Neoplastic Oncology chemistry 030220 oncology & carcinogenesis DNA methylation Cancer research Female Glioblastoma Genome-Wide Association Study Transcription Factors |
| Zdroj: | International Journal of Cancer. 145:3425-3435 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.32587 |
| Popis: | DNA methylation has long been recognized as a tumor-promoting factor when aberrantly regulated in the promoter region of genes. However, the effect of intragenic DNA methylation remains poorly understood on the clinical aspects of cancer. Here, we first evaluated the significance of intragenic DNA methylation for survival outcomes of cancer patients in a genome-wide manner. Glioblastoma patients with hypermethylated intragenic regions exhibited better survival than hypomethylated patients. Enrichment analyses of intragenic DNA methylation profiles with epigenetic signatures prioritized the intragenic DNA methylation of ZMIZ1 as a possible glioblastoma prognostic marker that is independent of MGMT methylation in IDH1 wild-type patients. This intragenic region harbored molecular signatures of alternative transcription across many cell types. Furthermore, we found that the intragenic region of ZMIZ1 can serve as a molecular marker in multiple cancers including astrocytomas, bladder cancer and renal cell carcinoma according to DNA methylation status. Finally, in vitro and in vivo experiments uncovered the role of ZMIZ1 as a driver of tumor cell migration. Altogether, our results identify ZMIZ1 as a prognostic marker in cancer and highlight the clinical significance of intragenic methylation in cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text