Alzheimer's disease susceptibility genes in low-grade glioma

Abstract

Background and Aim: Cognitive deficits in low-grade glioma are well documented. Patients with glioma who are carriers of the apolipoprotein E (APOE) e4 allele may have increased memory problems and executive dysfunction. While APOE is ranked the number one Alzheimer's disease (AD) susceptibility gene, many other susceptibility genes have been identified in genome-wide association studies. This study aimed to analyze the expression of APOE and the next 23 ranked AD susceptibility genes in malignant gliomas to identify significantly co-occurrent genes. Materials and Methods: To identify the most important AD susceptibility genes, the AlzGene database ( http://www.alzgene.org/ ) was consulted, which displays this information and regularly updates it. To analyze AD susceptibility genes in glioma, The Cancer Genome Atlas, a project begun in 2005, was used to catalog genetic mutations responsible for cancer, employing genome sequencing and bioinformatics. The cBioPortal for cancer genomics and the UCSC Xena browser were used to analyze the data in The Cancer Genome Atlas. Results: APOE and CD33 were the only significantly co-occurrent genes in 514 low-grade glioma tumor samples. APOE was altered in 1.8% of cases and CD33 in 3%. Heatmap indicates that the two genes tend to coexpress. The most common alteration was deep deletion. The cBioPortal and the Xena browser cannot distinguish or identify the alleles of APOE or CD33. Conclusions: AD patients with one or more APOE e4 alleles, having one or more copies of the CD33 risk allele (rs3865444 C), are at increased risk of cognitive decline compared to APOE E4 carriers, no doubt reflected by the co-occurrence of APOE and CD33 alterations in the gliomas. Better understanding of the interaction of genes and cognition in glioma patients may lead to new opportunities to personalize cancer therapy.