Dataset Information

Identification of Dysregulated Competitive Endogenous RNA Networks Driven by Copy Number Variations in Malignant Gliomas.

ABSTRACT: Gliomas represent 80% of malignant brain tumors. Because of the high heterogeneity, the oncogenic mechanisms in gliomas are still unclear. In this study, we developed a new approach to identify dysregulated competitive endogenous RNA (ceRNA) interactions driven by copy number variation (CNV) in both lower-grade glioma (LGG) and glioblastoma multiforme (GBM). By analyzing genome and transcriptome data from The Cancer Genome Atlas (TCGA), we first found out the protein coding genes and long non-coding RNAs (lncRNAs) significantly affected by CNVs and further determined CNV-driven dysregulated ceRNA interactions by a customized pipeline. We obtained 13,776 CNV-driven dysregulated ceRNA pairs (including 3,954 mRNAs and 306 lncRNAs) in LGG and 262 pairs (including 221 mRNAs and 11 lncRNAs) in GBM, respectively. Our results showed that most of the ceRNA interactions were weakened by CNVs in both LGG and GBM, and many CNV-driven genes shared the same ceRNAs in the dysregulated ceRNA networks. Functional analysis indicated that the CNV-driven ceRNA network involved in some important mechanisms of tumorigenesis, such as cell cycle, p53 signaling pathway and TGF-beta signaling pathway. Further investigation of the ceRNA pairs in the communities from the dysregulated ceRNA network revealed more detailed biological functions related to the oncogenesis of malignant gliomas. Moreover, by exploring the association of CNV-driven ceRNAs with prognosis and histological subtype, we found that the copy number status of MTAP, KLHL9, and ELAVL2 related to the overall survival in LGG and showed high correlation with histological subtype. In conclusion, this study provided new insight into the molecular mechanisms and clinical biomarkers in gliomas.

SUBMITTER: Xu J

PROVIDER: S-EPMC6827427 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of Dysregulated Competitive Endogenous RNA Networks Driven by Copy Number Variations in Malignant Gliomas.

Xu Jinyuan J Hou Xiaobo X Pang Lin L Sun Shangqin S He Shengyuan S Yang Yiran Y Liu Kun K Xu Linfu L Yin Wenkang W Xu Chaohan C Xiao Yun Y

Frontiers in genetics 20191025

Gliomas represent 80% of malignant brain tumors. Because of the high heterogeneity, the oncogenic mechanisms in gliomas are still unclear. In this study, we developed a new approach to identify dysregulated competitive endogenous RNA (ceRNA) interactions driven by copy number variation (CNV) in both lower-grade glioma (LGG) and glioblastoma multiforme (GBM). By analyzing genome and transcriptome data from The Cancer Genome Atlas (TCGA), we first found out the protein coding genes and long non-co ...[more]

PMID: 31719831

Similar Datasets

Project description:ContextFine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management.ObjectiveOur hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification.DesignOur study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and follicular variant PTCs (FVPTCs), the three subtypes most commonly associated with inconclusive preoperative cytopathology.SettingTissue and FNA samples were obtained at an academic tertiary referral center.PatientsCases were identified that underwent partial or complete thyroidectomy for malignant or indeterminate thyroid lesions between 2000 and 2008 and had adequate snap-frozen tissue.InterventionsPairs of tumor tissue and matching normal thyroid tissue-derived DNA were compared using 550K single-nucleotide polymorphism arrays.Main outcome measureStatistically significant differences in CNV patterns between tumor subtypes were identified.ResultsSegmental amplifications in chromosomes (Ch) 7 and 12 were more common in FAs than in PTCs or FVPTCs. Additionally, a subset of FAs and FVPTCs showed deletions in Ch22. We identified the 5 CNV-associated genes best at discriminating between FAs and PTCs/FVPTCs, which correctly classified 90% of cases. These 5 Ch12 genes were validated by quantitative genomic PCR and gene expression array analyses on the same patient cohort. The 5-gene signature was then successfully validated against an independent test cohort of benign and malignant tumor samples. Finally, we performed a feasibility study on matched FA-derived intraoperative FNA samples and were able to correctly identify FAs harboring the Ch12 amplification signature, whereas FAs without amplification showed a normal Ch12 signature.ConclusionsThyroid tumor subtypes possess characteristic genomic profiles that may further our understanding of structural genetic changes in thyroid tumor subtypes and may lead to the development of new diagnostic biomarkers in FNA samples.

Dataset Information

Identification of Dysregulated Competitive Endogenous RNA Networks Driven by Copy Number Variations in Malignant Gliomas.

Publications

Identification of Dysregulated Competitive Endogenous RNA Networks Driven by Copy Number Variations in Malignant Gliomas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets