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Multiclonality and altered RFLP patterns for immunoglobulin heavy-chain and T-cell receptor genes in relapsing
J Lindh1, B Linderholm, A Lindström
1Institution of Oncology, University of Umeå, Sweden.
Background:
Alteration of morphological appearance as well as of clinical behaviour is common in relapsing non-Hodgkin's lymphomas. The aim of this study was to investigate the stability of the genes encoding the immunoglobulin heavy-chain and the T-cell receptor during the course of the disease in relapsing non-Hodgkin's lymphomas.
Material And Methods:
Nineteen patients with relapsed or progressive non-Hodgkin's lymphomas were analysed with respect to alterations of the restriction fragment length polymorphism (RFLP) pattern for Ig heavy chain (IgH) using probes for the C mu and J regions and for T-cell receptor (T-beta, T-gamma chain) genes. DNA was extracted from tumour material taken at different occasions during the course of the disease.
Results:
All 19 cases showed clonal rearrangements of the IgH locus, and 2 cases showed simultaneous rearrangement of the genes coding for the T-cell receptors. Three or more rearranged bands, indicating more than one malignant clone, were detected in 1 case at the time of the diagnosis and in 5/19 (26%) cases in DNA from samples taken at relapse, all 6 cases showing discordant or transformed morphology. Altogether, in 11 out of 19 cases (58%), changes of the IgH rearrangement pattern could be visualized by RFLP. In all these cases except one, the new RFLP pattern included at least one rearranged band from the pattern of the first taken sample. In one case a clonal T-gamma receptor gene rearrangement was detected in a diagnostic sample but not in a sample taken at relapse. In 4 out of 6 cases with transformed lymphomas, clonal changes were observed at time of transformation. Evolution of clones with different RFLP patterns in different compartments were observed in 1 out of 6 studied cases.
Conclusions:
The present study illustrates that non-Hodgkin's lymphomas are unstable in their IgH genome. The observations of clonal evolution, multiclonality, and different clones in different compartments offer an explanation to the troublesome situation when treating relapsed lymphomas.