Comparable Genomic Copy Number Aberrations Differ across Astrocytoma Malignancy Grades.
Nives Pećina-ŠlausAnja KafkaKristina Gotovac JerčićMonika LogaraAnja BukovacRobert BakarićFran BorovečkiPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- copy number
- mitochondrial dna
- toll like receptor
- pi k akt
- genome wide
- papillary thyroid
- signaling pathway
- dna methylation
- cell proliferation
- immune response
- nuclear factor
- inflammatory response
- binding protein
- oxidative stress
- electronic health record
- gene expression
- lymph node metastasis
- high resolution
- childhood cancer
- young adults
- single cell
- high density
- nucleic acid
- innate immune