Immunoglobulin VH gene replacements in a T-cell lymphoblastic lymphoma

We have analysed the rearrangement status of the immunoglobulin heavy (IgH) chain locus during progression of a T-cell lymphoblastic lymphoma displaying multiple IgH rearrangements as demonstrated by variable heavy (VH) gene family specific polymerase chain reaction (PCR) analysis. The tumor was found to undergo diversification at the IgH locus between diagnosis and relapse through a mechanism of VH to VHDJH replacement. In subsets of the tumor at relapse, two separate VH gene segments were found to have replaced the VH gene utilized by a VHDJH rearrangement identified at diagnosis. The observed VH gene replacement events appear to have been mediated by a heptamer sequence homologous to the heptamer of the recombination signal sequence (RSS) located internally in the VH gene segment. These results support the notion that VH replacements contribute to the diversification of immunoglobulin genes.