title: Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor.
abstract: We identified gene expression signatures predicting responsiveness to a Kinesin-5 (KIF11) inhibitor (Kinesin-5i) in cultured colon tumor cell lines. Genes predicting resistance to Kinesin-5i were enriched for those from chromosome 20q, a region of frequent amplification in a number of tumor types. siRNAs targeting genes in this chromosomal region identified AURKA, TPX2 and MYBL2 as genes whose disruption enhances response to Kinesin-5i. Taken together, our results show functional interaction between these genes, and suggest that their overexpression is involved in resistance to Kinesin-5i. Furthermore, our results suggest that patients whose tumors overexpress AURKA due to amplification of 20q will more likely resist treatment with Kinesin-5 inhibitor, and that inactivation of AURKA may sensitize these patients to treatment.
authors.affiliation: Rosetta Inpharmatics LLC, a wholly-owned subsidiary of Merck and Co., Inc., Seattle, WA 98109, USA. aimee_ jackson@merck.com
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Jackson
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Sumire
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Teresa
authors.initials: T
authors.lastname: Ward
authors.forename: Matthew
authors.initials: M
authors.lastname: Biery
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bartz
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley