Abstract
A collection of intracranial astrocytomas of different malignancy grades was analyzed for copy number aberrations (CNA) in order to identify regions that are driving cancer pathogenesis. Astrocytomas were analyzed by Array Comparative Genomic Hybridization (aCGH) and bioinformatics utilizing a Bioconductor package, Genomic Identification of Significant Targets in Cancer (GISTIC) 2.0.23 and DAVID software. Altogether, 1438 CNA were found of which losses prevailed. On our total sample, significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11, 22q12.3 remained significant even at 0.05 q-value. When divided into malignancy groups, the regions identified as significantly deleted in high grades were: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, while amplified 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 their involvement in early stages of tumorigenesis. Significantly enriched pathways were: PI3K-Akt, Cytokine-cytokine receptor, the nucleotide-binding oligomerization domain (NOD)–like receptor, Jak-STAT, retinoic acid-inducible gene (RIG)-I-like receptor and Toll-like receptor pathways. HPV and herpex simplex infection and inflammation pathways were also represented. The present study brings new data to astrocytoma research amplifying the wide spectrum of changes that could help us identify the regions critical for tumorigenesis.
Highlights
Despite the advances in astrocytoma genetics and molecular characterization, many questions about the biology of these most common primary central nervous system tumors remain unanswered
Grade III astrocytoma accounts for 4% of all brain tumors while glioblastoma astrocytoma accounts for 45–50% of all primary malignant brain tumors
Our Array Comparative Genomic Hybridization (aCGH) results showed 1438 copy number aberrations (CNA) found across astrocytomas of different malignancy grades, including 21 amplifications, 397 gains, 929 losses and 91 deletions
Summary
Despite the advances in astrocytoma genetics and molecular characterization, many questions about the biology of these most common primary central nervous system tumors remain unanswered. The heterogeneity of their histological features is accompanied with marked genetic and genomic heterogeneity [1,2]. Grades differ in tumor histology, growth potential, and tendency for progression, age distribution, behavior and prognosis. Astrocytomas grade I (pilocytic) typically shows that benign clinical behavior and malignant progression is extraordinarily rare, describing it as a benign tumor. The highly invasive nature of glioblastoma makes it a deadly malignant tumor that is still untreatable [11]
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