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Low rate of somatic hypermutations characterize progressive B‐cell lymphomas
Author(s) -
Rosenquist Richard,
Lindström Anita,
Li AiHong,
Roos Göran,
Lindh Jack,
Holmberg Dan
Publication year - 1998
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1998.tb01080.x
Subject(s) - biology , microbiology and biotechnology , gene rearrangement , single strand conformation polymorphism , minimal residual disease , gene , somatic hypermutation , mutation , point mutation , immunoglobulin heavy chain , mutant , somatic cell , polymerase chain reaction , genetics , antibody , cancer research , b cell , leukemia
Immunoglobulin heavy (IgH) chain gene rearrangements were characterized in 40 samples from 15 patients with B‐cell lymphomas at different time points during tumour progression. Using polymerase chain reaction (PCR) amplification and single strand conformation polymorphism (SSCP) analysis of variable heavy (V H ) chain gene segments, we found that 6 cases displayed alterations in their IgH chain rearrangements at relapse. These alterations were mainly observed in follicular or transformed lymphomas, but no association to clinical features was found. Nucleotide sequence analysis revealed a low frequency of mutations in 3 cases, whereas 1 case displayed an extensive mutation rate in a compartment with transformed morphology at relapse. The mutations observed most probably resulted from somatic hypermutations. Further, the mutations were scattered randomly over the V 11 gene segment and no significant bias favouring amino acid substitutions was observed in 3 cases, suggesting that the tumour cells had not been subjected to antigen‐driven selection. In 1 case, however, the mutation pattern indicated that the tumour cells had been affected by an antigen selection process. In the 2 remaining cases, the original V H DJ H rearrangement could no longer be detected by V H gene family specific PCR at relapse, but using primers specific for the framework region 2 or 3 altered rearrangements were demonstrated, implying that mutations had been introduced in framework region 1. However, the majority of the tumour cell clones analysed were relatively stable during tumour progression, which make them eligible for analysis of minimal residual disease using the V H gene regions as molecular markers.