title: Chromosome microdissection identifies genomic amplifications associated with drug resistance in a leukemia cell line: an approach to understanding drug resistance in cancer.
abstract: A significant problem encountered in the treatment of cancer patients is that cancer cells often evolve resistance to chemotherapeutic agents. One of the mechanisms responsible for drug resistance is gene amplification. The study of the behavior of genes conferring drug resistance is very important to determine future treatments for cancer patients that will minimize the effect of gene amplification. One of the best methods to investigate this phenomenon is to use chromosome microdissection to directly access the amplified gene or genes. In the present study, chromosome microdissection and fluorescent in-situ hybridization (FISH) were applied for the identification of genes residing in a homogeneously staining region (HSR) in drug-resistant cell sublines developed by treatment of the T-cell leukemia cell line CCRF-CEM with increasing levels of the anthracycline, epirubicin. We have demonstrated that the selection by epirubicin actually elevated the level of the multidrug resistance-associated protein (MRP1) gene. We argue that the breakage fusion bridge (B-F-B) cycle offers a plausible explanation for this amplification. The DNA prepared from the amplified regions by chromosome microdissection provides a resource for future investigations looking for the possible presence of novel genes contributing to drug resistance.
authors.affiliation: Clinical Genetic Department, National Research Institute of Genetic Engineering and Biotechnology (NIGEB), Pazhoohesh Boulevard, Tehran-Keraj Highway, Tehran, Iran. frouz@ncgeb.ac.ir
authors.forename: Frouzandeh
authors.initials: F
authors.lastname: Mahjoubi
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hill
authors.forename: Greg B
authors.initials: GB
authors.lastname: Peters
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002877:Chromosomes, Human; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015251:Epirubicin / Q000494:pharmacology; D005784:Gene Amplification; D019450:Genes, MDR; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D042282:Microdissection; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D015251:Epirubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1