Aberrant promoter methylation of previously unidentified target genes is a common abnormality in medulloblastomas–Implications for tumor biology and potential clinical utility
| Autor: | Zunyan Dai, Xin Gao, Fred A. Wright, Michael C. Frühwald, Christoph Plass, Douglas A. Balster, Stephan M. Tanner, M. Sue O'Dorisio |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Cancer Research Adolescent Restriction landmark genomic scanning Cell Cycle Proteins Biology Genetics medicine Tumor Cells Cultured Humans Neuroectodermal Tumors Primitive Epigenetics Gene Silencing Cerebellar Neoplasms Child Promoter Regions Genetic neoplasms Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15 Tumor Suppressor Proteins Single-strand conformation polymorphism Promoter Methylation DNA Methylation medicine.disease Cadherins Prognosis Molecular biology Survival Rate CpG site Primitive neuroectodermal tumor Child Preschool DNA methylation Cancer research CpG Islands Female Carrier Proteins Medulloblastoma |
| Popis: | Medulloblastomas exhibit an array of diverse cytogenetic abnormalities. To evaluate the significance of epigenetic rather than genetic lesions in medulloblastomas and other primitive neuroectodermal tumors (PNETs) of the childhood CNS we performed a systematic analysis of gene specific and global methylation. Methylation-specific PCR detected no methylation for p15(INK4B), von Hippel Lindau and TP53 and only limited methylation for E-Cadherin and p16(INK4A) in tumors. The cell lines Daoy and MHH-PNET-5 in which the p16(INK4A) promoter was methylated did not express the gene, but demonstrated abnormalities by SSCP. Immunohistochemistry for p16 was negative in all examined normal cerebella and medulloblastomas. Using the technique of Restriction Landmark Genomic Scanning we detected methylation affecting up to 1% of all CpG islands in primary MB/PNETs and 6% in MB cell lines. Methylation patterns differed between medulloblastomas and PNETs. Examination of several methylated sequences revealed homologies to known genes and expressed sequences. Analysis of survival data identified seven of 30 hypermethylated sequences significantly correlating with poor prognosis. We suggest that DNA hypermethylation has an outstanding potential for the identification of novel tumor suppressors as well as diagnostic and therapeutic targets in MBs and other PNETs of the CNS. |
| Databáze: | OpenAIRE |
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