engleski

Exploring potential roles of genes annotated to malignant astrocytoma through datamining of cBioPortal database

Introduction: In order to identify regions that drive cancer pathogenesis and novel candidate genes for glioma, a cohort of 10 high-grade astrocytomas was analyzed for copy number aberrations and bioinformatics and validated in silico. Methods: Astrocytomas were analyzed by Array Comparative Genomic Hybridization (aCGH) using SurePrintG3 Human microarrays 4×180K (Agilent Technologies). Bioinformatics was performed utilizing Genomic Identification of Significant Targets in Cancer (GISTIC) 2.0.23 and DAVID softwares. Subsequently, the expression data of mRNA, protein and mutations for each annotated gene were explored through the cBioPortal web resource providing in silico validation. Results: GISTIC identified regions of aberration in grade III and IV tumors focusing on 0.25 q-value. The regions identified as significantly deleted were: 9p21.3 ; 17p13.2 ; 10q24.2 ; 14q21.3 ; 1p36.11 and 13q12.11, while amplified regions were: 3q28 ; 12q13.3 and 21q22.3. According to DAVID software those regions harbored 65 significantly over- represented genes that were assigned to a pathway or a functional category via gene annotation. Significantly enriched pathways were: PI3K-Akt, Cytokinecytokine receptor, NOD- like receptor, Jak-STAT, RIG-II-like receptor and Toll-like receptor pathways. Pathways involved in HPV and herpex simplex infection, as well as several pathways involved in inflammation, were also significantly represented in terms of the number of genes identified. Relevant candidate genes based on cBioPortal data were: C1QBP, CCNA1 CHUK, CLDN7, FGF8, FGF9, FGR, NFKB2, TRIM8 and YWHAE. Discussion: Genes mapped in narrow regions with altered DNA copy number may represent potential candidate tumor suppressor genes and oncogenes. cBioPortal compiles 7, 893 cancer cases from the 33 most recent The Cancer Genome Atlas (TCGA) studies. Our results identified alterations, pathways and genes that are biologically and functionally significant. Conclusion: The present study identifies candidate genes involved in the etiology of human astrocytoma providing a better understanding of the disease for future diagnostics and therapeutics.

glioblastoma ; candidate genes ; comparative genomic hybridization ; GISTIC 2.0.23 ; cBioPortal

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