DETECTION OF 11Q13 REARRANGEMENTS IN HEMATOLOGIC NEOPLASIAS BY DOUBLE-COLOR FLUORESCENCE IN-SITU HYBRIDIZATION

Rearrangements within the chromosome 11q13 region are frequent in hema tologic malignancies. 50% to 75% of mantle cell lymphomas (MCLs) carry a translocation t(11;14) (q13;q32). Using Southern blot analysis, a B CL1 breakpoint can be detected in approximately 50% of MCLs. It is not known whether other MCLs harbor also breakpoints at 11q13. Breakpoint s in this region not involved in t(11;14), are detected in chronic lym phocytic leukemia and acute myeloid leukemia. To detect and localize b reakpoints at 11q13 more accurately, we have developed fluorescence in situ hybridization using two probe sets of differently labeled cosmid s, symmetrically localized at either side of the major translocation c luster of BCL1. These probes span a region of 450 to 750 kb. We applie d this assay to a series of hematologic malignancies with 11q13 abnorm alities identified by classical cytogenetics. All four samples with a t(11;14) (q13;q32) showed dissociation of the differently colored sign als in metaphase and interphase cells, thereby indicating a chromosoma l break in the region defined by the probe sets. The frequency of abno rmal metaphase and interphase cells was comparable with that observed by banding analysis. No dissociation was observed in any of the 13 mal ignancies with other chromosomal 11q13 abnormalities, indicating that these chromosomal breaks occurred outside the 450- to 750-kb region co vered by the probes. One patient showed triplication and one patient s howed monoallelic loss of this region. The current data show that doub le-color fluorescence in situ hybridization is a simple and reliable m ethod for detection of the t(11;14)(q13;q32) in interphase cell nuclei and that it can be used to distinguish this translocation from other 11q13 rearrangements in hematologic malignancies. (C) 1996 by The Amer ican Society of Hematology.