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.