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Molecular cytogenetic delineation of deletions and translocations involving
chromosome band 7q22 in myeloid leukemias
K Fischer, S Frohling, SW Scherer, J McAllister Brown, C Scholl, S Stilgenbauer, LC Tsui, P Lichter and H Dohner
Medizinische Klinik, University of Heidelberg, Germany.
Loss of chromosome 7 (-7) or deletion of its long arm (7q-) are recurring
chromosome abnormalities in myeloid disorders, especially in
therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia
(t-AML). The association of -7/7q- with myeloid leukemia suggests that
these regions contain a novel tumor suppressor gene(s) whose loss of
function contributes to leukemic transformation or tumor progression. Based
on chromosome banding analysis, two critical regions have been identified:
one in band 7q22 and a second in bands 7q32-q35. We analyzed bone marrow
and blood samples from 21 patients with myeloid leukemia (chronic myeloid
leukemia, n = 2; de novo MDS, n = 4; de novo AML, n = 13; t-AML, n = 2)
that on chromosome banding analysis exhibited deletions (n = 19) or
reciprocal translocations (n = 2) of band 7q22 using fluorescence in situ
hybridization. As probes, we used Alu-polymerase chain reaction products
from 22 yeast artificial chromosome (YAC) clones that span chromosome bands
7q21.1-q32, including representative clones from a panel of YACs
recognizing a contiguous genomic DNA fragment of 5 to 6 Mb in band 7q22. In
the 19 cases with deletions, we identified two distinct commonly deleted
regions: one region within band 7q22 was defined by the two CML cases; the
second region encompassed a distal part of band 7q22 and the entire band
7q31 and was defined by the MDS/AML cases. The breakpoint of one of the
reciprocal translocations was mapped to 7q21.3, which is centromeric to
both of the commonly deleted regions. The breakpoint of the second
translocation, which was present in unstimulated bone marrow and
phytohemagglutinin-stimulated blood of an MDS patient, was localized to a
400-kb genomic segment in 7q22 within the deletion cluster of the MDS/AML
cases. In conclusion, our data show marked heterogeneity of 7q22 deletion
and translocation breakpoints in myeloid leukemias, suggesting the
existence of more than one pathogenetically relevant gene.
Volume 89,
Issue 6,
pp. 2036-2041,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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