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Blood, 15 January 2001, Vol. 97, No. 2, pp. 490-495
NEOPLASIA
Illegitimate switch recombinations are present in approximately
half of primary myeloma tumors, but do not relate to known prognostic
indicators or survival
P. Joy Ho,
Ross D. Brown,
Gregory J. Pelka,
Antony Basten,
John Gibson, and
Douglas E. Joshua
From the Institute of Haematology and Centenary
Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred
Hospital, Sydney, Australia.
The myeloma plasma cell is a postgerminal center, isotype-switched
B cell. Chromosomal translocations into immunoglobulin heavy chain
(IgH) switch regions, recombination sites in isotype switching, were
initially demonstrated in myeloma cell lines but only a limited number
of primary tumors. Molecular cytogenetics have since been applied to a
series of primary tumors, in which IgH translocations accounted for
many recurrent aberrations, among numerous nonrecurrent changes of
unknown significance. This study, therefore, examined primary myeloma
for IgH switch translocations using an established Southern blot assay
that detected illegitimate switch recombinations. Sensitivity of the
method was established by confining the analysis to 21 samples (4 stable, 17 progressive disease) with demonstrable legitimate isotype
switches, of a total of 60 samples. Illegitimate recombinations were
found in 12 or 57% (1 stable, 11 progressive) of 21 samples,
comparable with estimates by molecular cytogenetics. The presence of
switch translocations was supported by demonstrating up-regulated
expression in myeloma marrow of cyclin D1 and fibroblast growth factor
receptor 3 (FGFR3), candidate oncogenes on chromosomes 11q13 and 4p16,
respectively. Illegitimate switches were detected most frequently in
Sµ, with more than one region involved in 6 cases. Although these
results confirmed the presence of switch translocations in primary
myeloma, their absence in 43% of cases may imply heterogeneity of
pathogenesis. In progressive disease, there was no significant
difference between patients with and without illegitimate switches in
survival, nor the prognostic indicators of  2
microglobulin (2m) and serum thymidine kinase (STK).
Hence IgH switch translocations as a single entity are unlikely to be a
feature of disease progression or have prognostic significance.
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