Interphase fluorescence in situ hybridization assay for the detection of 3q21 rearrangements in myeloid malignancies

In myeloid malignancies, chromosome rearrangements involving band 3q21 are associated with a particularly poor prognosis of the disease. Their sensiti ve and unequivocal detection is therefore of great clinical importance. In this report, we describe the establishment of an interphase fluorescence in situ hybridization (FISH) assay that complements classical cytogenetic ana lysis in the diagnosis of such aberrations. PACs that map centromeric and t elomeric of known 3q21 breakpoints were labeled with different fluorescent dyes, and the separation of the normally colocalizing signals was used as a n indicator of the presence of a 3q21 rearrangement. Two cell lines and 10 primary samples from myeloid leukemia and myelodysplastic syndrome (MDS) pa tients with 3q21 rearrangements were investigated using the newly establish ed method. The rate of false positivity was determined in 27 control sample s from patients with various types of myeloid malignancies. In addition to providing a sensitive and rapid test for the detection of 3q21 aberrations, the interphase FISH assay yields preliminary information about the localiz ation of individual breakpoints. Six of the 10 breakpoints in the patient s amples map to an only recently described breakpoint cluster region (BCR) 60 kb centromeric of the originally reported 3q21 BCR. These findings may con tribute to the understanding of the molecular basis of the clinical feature s associated with 3q21 rearrangements. (C) 2001 Wiley-Liss, Inc.