title: Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines.
abstract: Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. In this study high-level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) were created, and comparative genomic hybridisation was used to identify genomic regions associated with resistance to docetaxel. MCF-7 resistant cells showed an amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of chromosomes 6p, 10q11.2-qter and 12p. MDA-MB-231 resistant cells showed a gain of chromosomes 5p, 7q11.1-q35, 9, and loss of chromosomes 4, 8q24.1-qter, 10, 11q23.1-qter, 12q15-q24.31, 14q and 18. Whole chromosome paints confirmed these findings. Amplification of 7q21 and loss of 10q may represent a common mechanism of acquired docetaxel resistance in breast cancer cells. This study is the first description of a genomic approach specifically to identify genomic regions involved in resistance to docetaxel.
authors.affiliation: School of Medicine, College of Life Sciences and Medicine, University of Aberdeen, Medical School, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: McDonald
authors.forename: David A J
authors.initials: DA
authors.lastname: Stevenson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Moir
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hutcheon
authors.forename: Neva E
authors.initials: NE
authors.lastname: Haites
authors.forename: Steven D
authors.initials: SD
authors.lastname: Heys
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Schofield
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D009693:Nucleic Acid Hybridization; D043823:Taxoids / Q000627:therapeutic use*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D043823:Taxoids; D000077143:Docetaxel; D014700:Verapamil