title: MicroRNA gene dosage alterations and drug response in lung cancer.
abstract: Chemotherapy resistance is a key contributor to the dismal prognoses for lung cancer patients. While the majority of studies have focused on sequence mutations and expression changes in protein-coding genes, recent reports have suggested that microRNA (miRNA) expression changes also play an influential role in chemotherapy response. However, the role of genetic alterations at miRNA loci in the context of chemotherapy response has yet to be investigated. In this study, we demonstrate the application of an integrative, multidimensional approach in order to identify miRNAs that are associated with chemotherapeutic resistance and sensitivity utilizing publicly available drug response, miRNA loci copy number, miRNA expression, and mRNA expression data from independent resources. By instigating a logical stepwise strategy, we have identified specific miRNAs that are associated with resistance to several chemotherapeutic agents and provide a proof of principle demonstration of how these various databases may be exploited to derive relevant pharmacogenomic results.
authors.affiliation: British Columbia Cancer Research Centre, Vancouver, BC, Canada. kenfield@bccrc.ca
authors.forename: Katey S S
authors.initials: KS
authors.lastname: Enfield
authors.forename: Greg L
authors.initials: GL
authors.lastname: Stewart
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Pikor
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Alvarez
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.forename: Raj
authors.initials: R
authors.lastname: Chari
mesh_terms: D045744:Cell Line, Tumor; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger