ZNF-mediated resistance to imatinib mesylate in gastrointestinal stromal tumor.

ABSTRACT: Although imatinib mesylate (IM) has transformed the treatment of gastrointestinal stromal tumors (GIST), many patients experience primary/secondary drug resistance. In a previous study, we identified a gene signature, consisting mainly of Kruppel-associated box (KRAB) domain containing zinc finger (ZNF) transcriptional repressors that predict short-term response to IM. To determine if these genes have functional significance, a siRNA library targeting these genes was constructed and applied to GIST cells in vitro. These screens identified seventeen "IM sensitizing genes" in GIST cells (sensitization index (SI) <0.85 ratio of drug/vehicle) with a false discovery rate (FDR) <15%, including twelve ZNF genes, the majority of which are located within the HSA19p12-13.1 locus. These genes were sh

SUBMITTER: Rink L 

PROVIDER: S-EPMC3556080 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature