Immunoglobulin heavy variable (IgHV) gene mutation and micro-RNA expression in Burkitt’s lymphoma at Moi Teaching and Referral Hospital in Western Kenya

Abstract

Introduction: Burkitt’s lymphoma (BL) is a virus associated childhood B-cell cancer common in Eastern Africa. Continued survival of B-cells in germinal centres depend on expression of high affinity immunoglobulins (Ig) to complementary antigens by somatic hypermutation of Ig genes. Cellular microRNAs, non-coding RNAs have been reported to play role in cell cycle regulation. Both viral antigen dependent mutation and micro-RNA expression maybe involved in BL pathogenesis. Objective: To describe immunoglobulin heavy variable (IgHV) rearrangement and micro-RNA expressions in BL tumours. Methods: Genomic DNA were extracted and purified from BL tissue blocks at Moi Teaching and Referral Hospital, before amplification using IgHV consensus primers and sequencing. The sequences were then aligned with germline alleles in IMGT/ V-QUEST® database. Total RNA extracted from tissue blocks and cell lines were used to determine relative expression of hsa miR-34a and hsa-miR-127. Results: In all tumours, allele alignment scores and number of mutations range were 89.2-93.2%, 15-24 respectively. The range of IgHV amino acid changes were higher in EBER-1+ (15-25) than EBER-1- (9-15). In MYC+ tumours, the relative expression were: hsa-miR-127(2.09);hsa-miR-34a (2.8) and MYC- hsa-miR-127 (1.2), hsa-miR-34a (1.0). Conclusion: B-cell in BL contained somatic mutated IgHV gene and upregulated cellular microRNAs with possible pathogenetic role(s}