Allelic fusion of DNA topoisomerase II alpha and retinoic acid receptor alpha genes in adriamycin-resistant p388 murine leukemia revealed by fluorescence in situ hybridization.
Fluorescence in situ hybridization (FISH) analysis of metaphase and decondensed free chromatin fibers from Adriamycin (ADR)-sensitive and ADR-resistant murine cells demonstrated a close juxtaposition of topoisomerase II alpha (Top2a) and retinoic acid receptor alpha (Rara) genes in adjacent chromatin in the drug-resistant cells, and a close but separate genetic proximity in normal murine chromatin. This provides physical evidence that the chromosome 11 allelic rearrangement resulting in a chimeric truncated Top2a/Rara transcript in the ADR-resistant cells is due to a novel fusion of the Topo2a and Rara genes. This is the first description of a Rara gene disruption in cells selected for antineoplastic drug resistance.
Squire
J A
JA
Department of Pathology and Laboratory Medicine, University of Toronto, Canada.
McPherson
J P
JP
Beatty
B G
BG
Goldenberg
G J
GJ
D000483:Alleles; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000951:Antigens, Neoplasm; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D017404:In Situ Hybridization, Fluorescence; D007527:Isoenzymes / Q000235:genetics*; D007941:Leukemia P388 / Q000188:drug therapy / Q000235:genetics*; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011995:Recombination, Genetic; D013234:Stem Cells; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D000075223:Poly-ADP-Ribose Binding Proteins; D018168:Receptors, Retinoic Acid; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II; C000618812:Top2a protein, mouse