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- W2017101784 abstract "Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability (CIN) and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G2/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC." @default.
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- W2017101784 date "2008-11-15" @default.
- W2017101784 modified "2023-09-25" @default.
- W2017101784 title "AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma" @default.
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- W2017101784 doi "https://doi.org/10.4161/cc.7.22.7042" @default.
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