V(H) gene analysis of Burkitt's lymphoma in children from north-western Iran.
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 V(H) genes were amplified from 6/12 of the tumour masses and all of these were derived from the V(H)3 family, with 4/6 being derived from the most commonly used V(H)3 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 V(H) 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 V(H) 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.
Chapman
C J
CJ
Tenovus Laboratory, Southampton University Hospitals, UK.
Wright
D
D
Feizi
H P
HP
Davis
Z
Z
Stevenson
F K
FK
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001402:B-Lymphocytes / Q000473:pathology; D002051:Burkitt Lymphoma / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017403:In Situ Hybridization; D007492:Iran / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics*
D007135:Immunoglobulin Variable Region