engleski

Genomic copy number aberrations found in astrocytoma and their validation through cBioPortal database

Astrocytic tumors show great heterogeneity in terms of genetic alterations, morphology and behavior. The objective of our study was to discover genomic copy number aberrations (CNA) that are constant across astrocytoma grades, but also those that are specific for progression. In order to identify regions that are driving cancer pathogenesis and novel candidate genes, a cohort of 14 astrocytomas was 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 cBioPortal web resource providing in silico validation. Altogether, 1438 CNA were found of which losses prevailed. GISTIC identified regions of aberration focusing on 0.25 q-value. Significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11 and 22q12.3 remained significant even at 0.05 q- value. The significantly deleted regions in high grades were: 9p21.3 ; 17p13.2 ; 10q24.2 ; 14q21.3 ; 1p36.11 and 13q12.11, while amplifications were: 3q28 ; 12q13.3 and 21q22.3. Low grades comprised significant deletions at 3p14.3 ; 11p15.4 ; 15q15.1 ; 16q22.1 ; 20q11.22 and 22q12.3 indicating early events. According to DAVID gene annotation software the above regions harbored 65 significantly over-represented genes that were assigned to a pathway or a functional category. Significantly enriched pathways were: PI3K-Akt, Cytokine-cytokine receptor, NOD-like receptor, Jak-STAT, RIG-I-like receptor and Toll-like receptor pathways. Pathways involved in HPV and herpex simplex infections, and pathways involved in inflammation, were also represented. Candidate genes out of 65 over-represented based on Biocportal data were: C1QBP, CCNA1 CHUK, CLDN7, CLEC10A, FGF8, FGF9, FGR, HPS6, NFKB2, PIK3AP1, TRIM8 and YWHAE. Present study brings biologically and functionally significant genetic regions involved in etiology of human astrocytoma which may provide better understanding of the disease for future diagnostics and therapeutics.

astrocytic tumors ; copy number aberrations (CNA) ; GISTIC ; cBioPortal

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