FLUORESCENCE IN-SITU HYBRIDIZATION MAPPING OF TRANSLOCATIONS AND DELETIONS INVOLVING THE SHORT ARM OF HUMAN-CHROMOSOME-12 IN MALIGNANT HEMATOLOGIC DISEASES

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, a nd cosmid probes that we previously mapped and ordered on 12p12-13. FI SH analysis showed that the 12p13 translocation breakpoints were clust ered between two cosmids, D12S133 and D12S142, in 11 of 12 patients an d in one cell line. FISH analysis of 11 patients with deletions demons trated that the deletions were interstitial rather than terminal and t hat the distal part of 12p12, including the GDI-D4 gene and D12S54 mar ker, was deleted in all 11 patients. Moreover, FISH analysis showed th at cells from 3 of these patients contained both a del(12p) and a 12p1 3 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome ( YAC) clones that span all the 12p13 translocation breakpoints mapped b etween D12S133 and D12S142. They have inserts of human DNA between 1.3 9 and 1.67 Mb. Because the region between D12S133 and D12S142 also rep resents the telomeric border of the smallest commonly deleted region o f 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the o ther patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was delet ed. Thus, most 12p13 translocation breakpoints were clustered within t he sequences contained in the 1.39 Mb YAC and this YAC appears to incl ude the telomeric border of the smallest commonly deleted region. Whet her the same gene is involved in both the translocations and deletions is presently unknown. (C) 1994 by The American Society of Hematology.