SHORTENED TELOMERES INVOLVED IN A CASE WITH A JUMPING TRANSLOCATION AT 1Q21

The jumping translocation (JT) is a rare chromosomal abnormality in wh ich a specific chromosomal segment translocates onto the ends of vario us chromosomes (jumps). In most cases, the region distal to 1q21 jumps onto numerous different telomeres. Here we report a molecular study o f the JT involving 1q21 found in a patient with acute myelomonocytic l eukemia that had transformed from myelodysplastic syndrome (MDS). This is the first report describing the analysis of the molecular structur e of the JT. We demonstrated the presence of a stretch of telomeric re peats at the breakpoint by means of a fluorescence in situ hybridizati on experiment, molecular cloning, and nucleotide sequencing of the fus ed region. A significant amount of variant telomeric repeats (a telome ric sequence having one-base mismatch within the authentic telomeric r epeat TTAGGG) was found in this region. The variant telomeric repeat h as been shown to be present in the proximal region of telomeres and do es not perform telomeric functions by itself, Therefore, these results indicated that the telomeres had already been critically shortened wh en the jumps occurred. We suggest that the extended proliferation of c ancer cells during the premalignant stage, such as MDS, results in chr omosomal instability due to the loss of telomeric functions, (C) 1998 by The American Society of Hematology.