Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age
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Impact Journals LLC
Abstract
Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.
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Aneuploidy, Braf, Mdm2, Pilocytic astrocytoma, Plk2, Adult, Age factors, Astrocytoma, Biomarkers, tumor, Brain neoplasms, Child, Cohort studies, Female, Gene expression profiling, Humans, Male, Mutation, Neoplasm staging, Prognosis, Proto-oncogene proteins b-raf, Proto-oncogene proteins c-mdm2, Real-time polymerase chain reaction, Receptor, fibroblast growth factor, type 1, Reverse transcriptase polymerase chain reaction, Rna, messenger, Young adult, B raf kinase, Fibroblast growth factor receptor 1, Polo like kinase 2, Protein mdm2, Braf protein, human, Fgfr1 protein, human, Mdm2 protein, human, Messenger rna, Tumor marker, Aging, Article, Brain development, Brain tumor, Cancer survival, Cell cycle, Chromosome 11, Chromosome 5, Chromosome 6, Chromosome 7, Chromosome mutation, Copy number variation, Dna damage, Dna extraction, Gene amplification, Gene dosage, Gene expression, Gene frequency, Gene ontology, Genomic instability, Human, Microarray analysis, Pontine glioma, Progression free survival, Rna extraction, Rna sequence, Unfolded protein response, Age, Cancer staging, Classification, Cohort analysis, Comparative study, Genetics, Pathology, Real time polymerase chain reaction, Reverse transcription polymerase chain reaction