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Fluorescence in situ hybridization mapping of translocations and deletions
involving the short arm of human chromosome 12 in malignant hematologic
diseases
H Kobayashi, KT Montgomery, SK Bohlander, CN Adra, BL Lim, RS Kucherlapati, H Donis-Keller, MS Holt, MM Le Beau and JD Rowley
Department of Medicine, University of Chicago, IL.
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, and cosmid
probes that we previously mapped and ordered on 12p12-13. FISH analysis
showed that the 12p13 translocation breakpoints were clustered between two
cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line.
FISH analysis of 11 patients with deletions demonstrated that the deletions
were interstitial rather than terminal and that the distal part of 12p12,
including the GDI-D4 gene and D12S54 marker, was deleted in all 11
patients. Moreover, FISH analysis showed that cells from 3 of these
patients contained both a del(12p) and a 12p13 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 between D12S133 and D12S142. They have
inserts of human DNA between 1.39 and 1.67 Mb. Because the region between
D12S133 and D12S142 also represents the telomeric border of the smallest
commonly deleted region of 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 other patient, the YAC labeled the del(12p) chromosome more
weakly than the normal chromosome 12, suggesting that a part of the YAC was
deleted. Thus, most 12p13 translocation breakpoints were clustered within
the sequences contained in the 1.39 Mb YAC and this YAC appears to include
the telomeric border of the smallest commonly deleted region. Whether the
same gene is involved in both the translocations and deletions is presently
unknown.
Volume 84,
Issue 10,
pp. 3473-3482,
11/15/1994
Copyright © 1994 by The American Society of Hematology
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