CBMS-05 Biological and Pathological meaning of aneuploidy in mouse glioma stem sell

Abstract

Chromosomal instability (CIN) is a pathological condition where cells continuously mis-segregate chromosomes, producing aneuploid cells. CIN has been recognized as a hallmark of cancer, and its correlation with biological malignancy has been pointed out. Glioma cell line often reveals karyotype aberrations, and a variety of ploidy in the tumor tissue. However, several studies have indicated that aneuploidy is disadvantageous for proliferation or tumorigenesis, and these paradox prompt us to address the role of aneuploid cells in tumor specimens. Here, we adopted mouse glioma stem cell lineages and found that aneuploid population is increased in glioma stem cells in vitro. We also examined Aurora B at centromeres which is crucial for failsafe chromosome segregation and found its reduced activity in glioma stem cells, suggesting that insufficient Aurora B activity plays a causative role in CIN in glioma stem cells. Next, to investigate the tumorigenicity of aneuploid cells, we sorted the glioma stem cells depending on the karyotype pattern, and allografted into mouse brain. We found that the growth rate of diploid glioma stem cells was higher than others in vitro, and the probability of survival after allogeneic transplant was significantly lower in diploid groups. We will discuss the role of ploidy in glioma cells populations.