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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4116-4121
NEOPLASIA
Down-regulation of candidate tumor suppressor genes
within chromosome band 13q14.3 is independent of the
DNA methylation pattern in B-cell
chronic lymphocytic leukemia
Daniel Mertens,
Stephan Wolf,
Petra Schroeter,
Claudia Schaffner,
Hartmut Döhner,
Stephan Stilgenbauer, and
Peter Lichter
From the Abteilung "Organisation komplexer Genome,"
Deutsches Krebsforschungszentrum, Heidelberg, Germany; and Innere
Medizin III, University of Ulm, Ulm, Germany.
Loss of genomic material from chromosomal band 13q14.3 is the most
common genetic imbalance in B-cell chronic lymphocytic leukemia (B-CLL)
and mantle cell lymphoma, pointing to the involvement of this region in
a tumor suppressor mechanism. From the minimally deleted region, 3 candidate genes have been isolated, RFP2, BCMS, and BCMSUN. DNA sequence analyses have failed to detect
small mutations in any of these genes, suggesting a different
pathomechanism, most likely haploinsufficiency. We, therefore, tested
B-CLL patients for epigenetic aberrations by measuring expression of
genes from 13q14.3 and methylation of their promotor region.
RB1, CLLD7, KPNA3, CLLD6, and
RFP2 were down-regulated in B-CLL patients as compared with
B cells of healthy donors, with RFP2 showing the most
pronounced loss of expression. To test whether this loss of gene
expression is associated with methylation of CpG islands in the
respective promotor regions, we performed methylation-sensitive quantitative polymerase chain reaction analyses and bisulfite sequencing on DNA from B-CLL patients. No difference in the methylation patterns could be detected in any CpG island of the minimally deleted region. Down-regulation of genes within chromosomal
band 13q14.3 in B-CLL is in line with the concept of
haploinsufficiency, but this tumor-specific phenomenon is not
associated with DNA methylation.
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