CYTOGENETIC AND MOLECULAR DELINEATION OF THE SMALLEST COMMONLY DELETED REGION OF CHROMOSOME-5 IN MALIGNANT MYELOID DISEASES

Loss of a whole chromosome 5 or a deletion of its long arm (5q) is a r ecurring abnormality in malignant myeloid neoplasms. To determine the location of genes on 5q that may be involved in leukemogenesis, we exa mined the deleted chromosome 5 homologs in a series of 135 patients wi th malignant myeloid diseases. By comparing the breakpoints, we identi fied a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. Dis tal 5q contains a number of genes encoding growth factors, hormone rec eptors, and proteins involved in signal transduction or transcriptiona l regulation. These include several genes that are good candidates for a tumor-suppressor gene, as well as the genes encoding rive hematopoi etic growth factors (CSF2, IL3, IL4, IL5, and IL9). By using fluoresce nce in situ hybridization, we have refined the localization of these g enes to 5q31.1 and have determined the order of these genes and of oth er markers within 5q31. By hybridizing probes to metaphase cells with overlapping deletions involving 5q31, we have narrowed the critical re gion to a small segment of 5q31 containing the EGR1 gene. The five hem atopoietic growth factor genes and seven other genes are excluded from this region. The EGR1 gene was not deleted in nine other patients wit h acute myeloid leukemia who did not have abnormalities of chromosome 5. By physical mapping, the minimum size of the critical region was es timated to be 2.8 megabases. This cytogenetic map of 5q31, together wi th the molecular characterization of the critical region, will facilit ate the identification of a putative tumor-suppressor gene in this ban d.