VHgene analysis of Burkitt's lymphoma in children from north-western Iran

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Abstract
Cases of Burkitt's lymphoma (BL) from north‐western Iran were investigated for the usage and somatic mutational pattern of their immunoglobulin variable region genes. Potentially functional VH genes were amplified from 6/12 of the tumour masses and all of these were derived from the VH3 family, with 4/6 being derived from the most commonly used VH3 family member, V3‐23. All of the tumour sequences were mutated from their germline counterparts, to varying degrees, with a mean level of 5.8%, indicating that the cell of origin had encountered the germinal centre. Intraclonal sequence heterogeneity was also evident in 4/6 of the lymphomas, showing that the tumour cells had undergone further somatic mutation following neoplastic transformation. Analysis of the five potentially functional mutated VH sequences showed a significant clustering of replacement mutations in the complementarity‐determining region 2, consistent with a role for antigen in selection of tumour cell sequences. The pattern of extensive somatic mutation, and intraclonal variation, in these mainly EBV+ve tumours, was similar to that previously reported in VH sequences of EBV+ve endemic BL (eBL) and EBV−ve sporadic BL (sBL), with the mean level of somatic mutation lying between those reported for eBL (7.7%) and sBL (4.0%). However, VH gene bias and the distribution of mutations in the Iranian cases showed features which differed from those reported for endemic or sporadic BL.