Abstract
Chromosomal heterogeneity is a hallmark of most tumors and it can drive critical events as growth advantages, survival advantages, progression and karyotypic evolution. Medulloblastoma (MB) is the most common malignant central nervous system tumor in children. This work attempted to investigate chromosomal heterogeneity and instability profiles of two MB pediatric cell lines and their relationship with cell phenotype. We performed GTG-banding and cytokinesis-block micronucleus cytome assays, as well as morphological characterization, cell population doubling time, colony-forming efficiency, and chemo-sensitivity assays in two pediatric MB cell lines (UW402 and UW473). Both MB cells showed a high chromosomal heterogeneity. UW473 cells showed ~2 fold higher both clonal- and non-clonal chromosomal alterations than UW402 cells. Besides, UW473 showed two clonal-groups well-differentiated by ploidy level (<2n> and <4n>) and also presented a significantly higher number of chromosomal instability biomarkers. These results were associated with high morphological heterogeneity and survival advantages for UW473 and proliferation advantages for UW402 cells. Moreover, UW473 was significantly more sensitive to methotrexate, temozolomide and cisplatin while UW402 cells were more sensitive to doxorubicin. These data suggest that distinct different degrees of karyotypic heterogeneity and instability may affect neoplasic phenotype of MB cells. These findings bring new insights into cell and tumor biology.
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Acknowledgments
The authors thank Patrícia Vianna Bonini Palma, Camila Cristina de Oliveira Menezes Bonaldo, and Daiane Fernanda dos Santos, Hemocentro-FMRP-USP, Ribeirão Preto, Brazil, Brazil, for assistance with the flow cytometry. The authors also thank Coordenação para o Aperfeiçoamento de Pessoal em Nível Superior-Brazil (CAPES) and Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da FMRPUSP (FAEPA) for financial support.
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Castro-Gamero, A.M., Borges, K.S., Lira, R.C. et al. Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype. Cytotechnology 65, 871–885 (2013). https://doi.org/10.1007/s10616-012-9529-z
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DOI: https://doi.org/10.1007/s10616-012-9529-z