title: Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype.
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.
authors: Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil, amcgen@gmail.com.
authors: Angel Mauricio
authors: AM
authors: Castro-Gamero
authors: Kleiton Silva
authors: KS
authors: Borges
authors: Regia Caroline
authors: RC
authors: Lira
authors: Augusto Faria
authors: AF
authors: Andrade
authors: Paola Fernanda
authors: PF
authors: Fedatto
authors: Gustavo Alencastro Veiga
authors: GA
authors: Cruzeiro
authors: Ricardo Bonfim
authors: RB
authors: Silva
authors: Aparecida Maria
authors: AM
authors: Fontes
authors: Elvis Terci
authors: ET
authors: Valera
authors: Michael
authors: M
authors: Bobola
authors: Carlos Alberto
authors: CA
authors: Scrideli
authors: Luiz Gonzaga
authors: LG
authors: Tone