Early G    cyclin-dependent kinases as prognostic markers and potential therapeutic targets in XXXX .

@entity1 @entity14107 @entity5 @entity996 @entity8985 @entity1017 @entity20406 @entity420
PURPOSE: @entity1017 at 7q21 is a frequent event in @entity420 ( @entity420 ). However, this event has not been mapped with fine resolution in a large @entity420 cohort, and its association with clinical endpoints and functional relevance are unclear. EXPERIMENTAL DESIGN: We used a cohort of 116 @entity1 to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored. RESULTS: Amplification of the 7q21 region was observed in 35% of @entity5 with a focal, minimal amplicon containing six genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified @entity14107 ( @entity14107 ) as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low-level amplification (10%) was observed at the 12q13 region containing the @entity14107 homologue @entity8985 ( @entity8985 ). Both amplification and expression of @entity8985 correlated with poor survival. A combined model of both @entity14107 and @entity8985 expressions is a superior predictor of survival than either alone. Specific knockdown of @entity8985 and/or @entity14107 by siRNAs shows that they are required for proliferation of @entity420 cells and that their function is additive. @entity20406 targets the kinase activity of both molecules and suppresses proliferation and anchorage independence of @entity420 cells through activation of the @entity996 pathway. CONCLUSIONS: We suggest that @entity14107 is the driver of 7q21 amplification and that both @entity8985 and @entity14107 are prognostic markers and bona fide oncogenes in @entity420 . Targeting these molecules may constitute a viable new therapy for this disease.
