Incidence of potential glycosylation sites in immunoglobulin variable regions distinguishes between subsets of Burkitt's lymphoma and mucosa‐associated lymphoid tissue lymphoma

Abstract

Summary. Recently, a high incidence of novel N-glycosylation sites introduced by somatic mutation was observed in the immunoglobulin variable region genes of follicular lymphoma. As these are positively selected and are uncommon in normal B cells, they may have a role in tumour growth and behaviour. Sites are not characteristic of chronic lymphocytic leukaemia or myeloma, but are detectable in 50% of diffuse large cell lymphomas. Another feature of the variable region genes of certain lymphomas is ongoing somatic mutation. To determine whether glycosylation is associated with this phenomenon, we analysed variable region gene sequences of Burkitt's lymphoma (BL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Novel sites were common in endemic BL (82%) and in 4/5 patients with Iranian BL. However, sporadic BL had a lower incidence (43%). Patients with MALT lymphoma had a low frequency (9%) of novel sites, comparable to normal B cells. These findings distinguish glycosylation sites from ongoing mutation and may reflect different environmental influences on these tumours.

Universal N-glycosylation sites introduced into the B-cell receptor of follicular lymphoma by somatic mutation: a second tumorigenic event?

“…We have also observed sites in a proportion (B40%) of cases of DLBCL, and commonly (82%) in endemic Burkitt's lymphoma. 2 However, sites are only occasionally seen in mutated CLL and multiple myeloma. The same is true for available sequences of normal B cells (memory B cells or plasma cells) with comparable levels of SHM to FL.…”

“…Part of the reason for this is probably attributable to technical differences in the sensitivity of the V617F detection. Most other studies used sequencing, which can underestimate the proportion of positive patients, 2,6 whereas allele-specific PCR assay is capable of detecting a mutation present in 1-2% of cells. 6 Of the 17 V617F-negative PV cases of our series, only two were female (P ¼ 0.044, contingency w 2 ¼ 4.058).…”

“…To date, this mutation has not been reported in normal controls, lymphoid disorders or in patients with secondary erythrocytosis. [1][2][3][4][5][6][7][8][9][10] In this study, we have analyzed bone marrow or peripheral blood samples from 349 patients (PV, n ¼ 84; ET, n ¼ 243; IMF, n ¼ 22) referred to our diagnostic service for cytogenetic analysis and/or exclusion of the BCR-ABL fusion from several hospitals in the north of Spain between 1996 and 2005. Our study group thus includes the largest series of ET cases reported to date for JAK2 analysis.…”

Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins

“…These sequence motifs are introduced during somatic hypermutation and are characteristic only of FL and some germinal center tumors, being very infrequent in normal B cells, in chronic lymphocytic leukemia, or in myeloma (5). The frequency of motifs in FL-derived IGHV sequences deposited in the database was 55 of 70 (79%), as compared with 7 of 75 (9%) in normal somatically mutated B cells (4).…”

Variations in “rescuability” of immunoglobulin molecules from different forms of human lymphoma: implications for anti-idiotype vaccine development

“…This phenomenon might imply that the most crucial step in this strategy for producing Id vaccine is the biological stabilization of an Id-secreting hybridoma. This is a problem that, per se, is not easily surmountable when dealing with rescue fusions and might even accelerate the transition towards recombinant technologies [23,24] Finally, at the time of writing it is not clear whether the recent identification of acquired, potential glycosylation sites within the amino acid sequences of tumor-specific immunoglobulins [25][26][27] may have an impact on either idiotypic vaccination as a whole or the choice of the methods by which the Id-containing immunoglobulin is rescued.…”