Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Abstract

Splenic marginal zone lymphoma (SMZL) has been recognized as a distinctive type of small B cell lymphoma, and defined on the basis of its morphological, phenotypic, clinical and molecular characteristics. In spite of this, the borders of the entity, the homogeneity of the cases and the presumably cell origin of SMZL remain controversial issues. The frequency of mutation in the 5′ non-coding region of the bcl-6 gene has been used as a marker of germinal center derivation, which may be used to establish the molecular heterogeneity of different non-Hodgkin lymphoma (

IgV and bcl6 somatic mutation analysis reveals the heterogeneity of cutaneous B-cell lymphoma, and indicates the presence of undisclosed local antigens

“…Its expression is related with the formation of germinal center through an incompletely understood regulation of the balance between proliferation and apoptosis. 26,32 Bcl6 gene is frequently involved in translocations in 30-40% of large cell lymphoma and in 6-10% of FLs. 33,34 Bcl6 somatic mutations are described in germinal center (GC) and post-GC-derived lymphoma, probably caused by somatic mutation machinery acting on the 5 0 noncoding region of the bcl6 gene, due to its sequence homology with immunoglobulin gene.…”

“…Amplification conditions have been described previously. 26 PCR product was then purified (Microcon PCR, Millipore) and was subjected to a cycle-sequencing reaction, using PCR producing primers and two previously described internal primers, E1.10 and E1.11.…”

Immunoglobulin Heavy- And Light-chain Repertoire in Splenic Marginal Zone Lymphoma

“…In contrast to other B-cell lymphomas, no consistent or unique genetic lesion has been associated with SMZL. Furthermore, there is abundant cytogenetic and molecular evidence pointing to SMZL genetic heterogeneity and the existence of distinct subentities: with/without plasma cell differentiation, IG and BCL-6 somatic mutations (9)(10)(11)(12)(13)(14)(15), allelic loss at chromosome 7q21-32 (16), and hepatitis C infection (17).…”

Analysis of BCL-6, CD95, PIM1, RHO/TTF and PAX5 mutations in splenic and nodal marginal zone B-cell lymphomas suggests a particular B-cell origin

“…2 The percentage of BLC-6 mutated SMZL cases (1/34 or 3%) was slightly inferior to that previously reported in 3 out of 22 mutated SMZL (13%). 8 This small variability could be explained by different criteria used to select cases. Of note, the mutation frequency in normal microdissected marginal zone B cells (35%) 8 seems then to be higher than in SMZL (3-13%), reflecting the marked heterogeneity of the B cells in marginal zone.…”

“…8 This small variability could be explained by different criteria used to select cases. Of note, the mutation frequency in normal microdissected marginal zone B cells (35%) 8 seems then to be higher than in SMZL (3-13%), reflecting the marked heterogeneity of the B cells in marginal zone. Our data indicate that marginal lymphomas derive essentially from a distinct BCL-6 unmutated subpopulation.…”