Delineation of multiple deleted regions in 7q in myeloid disorders

Loss of chromosome material due to deletions of the long arm of chromosome 7, del(7q), is a consistent finding in all types of myeloid disorders, inva riably associated with a poor prognosis. Two different segments, 7q22 and 7 q32-q33, have been implicated as critical regions of gene loss associated w ith these disorders. In the present study, we used fluorescence in situ hyb ridization (FISH) to characterize the 7q22 breakpoint of an apparently bala nced t(7;7)(p13:q22) in an acute myeloid leukemia patient. FISH analysis on bone marrow metaphases from this patient revealed that the sequence corres ponding to a series of three ordered cosmids from 7q22 was deleted from one of the der(7) chromosomes. These cosmids contain the human homologue of th e Drosophila homeobox gene cut (CUTL1) and span a region of approximately 1 50 kb, Although the proximal boundary of the deleted segment could not be e xactly defined, we estimate the size of this deletion to be approximately 5 00 kb. Subsequently, we carried out FISH studies using the CUTL1 cosmids on a further Ib patients with deletions of 7q and myeloid disorders. The sequ ence corresponding to at least two of the cosmids was deleted from the del( 7q) in 11 out of 14 cases with a proximal breakpoint within 7q22. Further d etailed FISH mapping in this series of 17 patients has identified two other nonoverlapping commonly deleted segments at 7q31-q32 and 7q33, respectivel y. These data confirm and refine other studies, implying that several diffe rent genes on 7q may be involved in the pathogenesis of myeloid diseases. G enes Chromosomes Cancer 25:384-392, 1999. (C) 1999 Wiley-Liss, Inc.