ALBERT

Description: Abstract 4135 The analysis of the immunoglobulin heavy chain variable (IGHV) genes in B-cell derived tumors can yield relevant pathogenic information; it contributes to the definition of the normal cell counterpart and in some neoplasias allowed the identification of subsets of stereotyped B cell receptors associated to different clinical/phenotypic features and outcome. According to the WHO 2008 Classification, Burkitt lymphomas (BL) derive from either germinal center (GC) or post GC B cells. This study was aimed at a comprehensive investigation of the IGH genes in BL; for that, 27 samples of BL were studied, including both pediatric (n=15) and adult (n=12) cases from the 3 clinical variants of the disease, namely endemic (n=1), sporadic (n=22) and immunodeficiency-associated (n=4). All the samples analyzed harbored in frame IGHV-D-J rearrangements, the great majority (96.3%) being functionally productive. The comparison of the IGH genes usage in BL with the normal repertoire found in CD5 neg B cells detected no differences concerning IGHJ and IGHD usage. However, the usage of IGHV genes was significantly different from that of the normal B cell counterpart (p=0.21). Genes like IGHV3-21 and IGHV5-a were only found in BL samples, with a frequency of 11.1% and 3.7% respectively. Other genes were overrepresented in BL with respect to normal B cells, namely IGHV2-70 (7.4% vs 1.3%), IGHV3-30 (11.1% vs 5.2%), IGHV4-34 (7.4% vs 4.3%), IGHV4-39 (11.1% vs 5.2%) and IGHV4-59 (14.8% vs 9.1%). These results pointed to a biased used of certain IGHV genes by BL cells. No preferential V-D-J rearrangement was detected and only 3 samples had common HCDR3 features, although with different V-D-J rearrangements. IGHV mutational load was calculated as the percentage of germline identity (GI). Most of the BL samples (70.4%) harbored mutated IGHV genes (