Project description:A comprehensive study is conducted to inspect the role and function of methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, as well as to test its potential as a novel prognostic biomarker. Using whole-genome microarray for transcriptome, the MBD3-mediated epigenetic regulation in glioma was profiled.
Project description:A comprehensive study is conducted to inspect the role and function of methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, as well as to test its potential as a novel prognostic biomarker. Using whole-genome microarray for transcriptome, the MBD3-mediated epigenetic regulation in glioma was profiled.
Project description:In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma.
Project description:Therapeutic screening of potential anticancer agents relies on representative cancer models. In vitro cell culture models have been long questioned to be representative for human malignant glioma. Therefore, in the present study genomic profiles of both short-term (2 weeks; n=8) and long-term (6 and 12 weeks; n=3) primary cell cultures and spheroid cultures were compared with their parental malignant gliomas. Cancer genomic profiles were obtained by 6400 BAC array comparative genomic hybridization. In 7 out of 8 short-term primary cell cultures, the genomic profiles clustered further from their parental tumors than the spheroid cultures. In 4 out of 8 samples, the changes were substantial and included chromosomal regions associated with prognosis and therapeutic response. The average correlation coefficients between parental tumor profiles and spheroid profiles was 0.89 (range: 0.79 to 0.97), whereas those between parental tumors and cell cultures was 0.62 (range: 0.10 to 0.96). In 2 out of 3 primary cell cultures progressive genetic changes appeared at 6 and 12 weeks after initial preservation, whereas the spheroid cultures were genetically stable throughout. It is concluded that the cancer genomic profile of primary cell cultures from malignant glioma is inconsistent with the parental tumorâs profile already after 2 weeks with subsequent progressive genetic changes. Because malignant glioma spheroids are genetically stable, biological characteristics of the parental tumor are better reflected. This indicates that the spheroid model is better for therapeutic screening. Keywords: comparative genomic hybridization Two in vitro culture models (primary cell culture and organotypic spheroid culture) and their parental tumor were compared in whole-genome DNA copy number profile. Malignant glioma surgical specimens from 8 patients were divided in parental tumor (T), primary cell culture (C) and organotypic spheroid culture (S). After 2 weeks, genomic DNA was extracted from culture harvests. For 3 of 8 surgical specimens (patient 55, 58, 60) cultures were extended to 6 and 12 weeks to determine DNA copy number changes in time. Primary cell culture harvests at 2, 6 and 12 weeks were named C1, C2, C3 and organotypic spheroid cultures harvests at 2, 6 and 12 weeks were named S1, S2, S3.
Project description:Data includes all available Affymetrix SNP data from a cohort of Pediatric malignant glioma samples, isolated from Formalin-fixed Paraffin embedded tissue. No clinical data is available. Copy number analysis of Affymetrix 250K Sty SNP arrays was performed for 28 pediatric malignant gliomas. The VN algorithm was used to generate the reference signal based on 48 Mapping 500k HapMap Trio Dataset template.