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Distinct Genomic Aberrations between Low-Grade and High-Grade Gliomas of Chinese Patients

Yunbo Li,Dapeng Wang,Lei Wang,Jinhai Yu,Danhua Du,Ye Chen,Peng Gao,Duen-mei Wang,Jun Yu,Feng Zhang,Shuanglin Fu

Published 2013 in PLoS ONE

ABSTRACT

Background Glioma is a type of tumor that develops in the central nerve system, mainly the brain. Alterations of genomic sequence and sequence segments (such as copy number variations or CNV and copy neutral loss of heterozygosities or cnLOH) are thought to be a major determinant of the tumor grade. Methods We mapped genomic variations between low-grade and high-grade gliomas (LGG and HGG) in Chinese population based on Illumina’s Beadchip and validated the results using real-time qPCR. Results At the cytoband level, we discovered: (1) unique losses in LGG on 5q, 8p and 11q, and in HGG on 6q, 11p, 13q and 19q; (2) unique gains in the LGG on 1p and in HGG at 5p, 7p, 7q and 20q; and (3) cnLOH in HGG only on 3q, 8q, 10p, 14q, 15q, 17p, 17q, 18q and 21q. Subsequently, we confirmed well-characterized oncogenes among tumor-related loci (such as EGFR and KIT) and detected novel genes that gained chromosome sequences (such as AASS, HYAL4, NDUFA5 and SPAM1) in both LGG and HGG. In addition, we found gains, losses, and cnLOH in several genes, including VN1R2, VN1R4, and ZNF677, in multiple samples. Mapping grade-associated pathways and their related gene ontology (GO) terms, we classified LGG-associated functions as “arachidonic acid metabolism”, “DNA binding” and “regulation of DNA-dependent transcription” and the HGG-associated as “neuroactive ligand-receptor interaction”, “neuronal cell body” and “defense response to bacterium”. Conclusion LGG and HGG appear to have different molecular signatures in genomic variations and our results provide invaluable information for the diagnosis and treatment of gliomas in patients with variable duration or diverse tumor differentiation.

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