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Follicular Lymphoma : BCL2, t(14;18) translocation

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About 90% of follicular lymphomas (FLs) show t(14;18)(q32;q21) translocation which places BCL2 gene on chromosome 18 under the influence of IGH promoter on chromosome 14 resulting in overexpression of BCL2. Rare cases have t(2;18)(p12;q21) which juxtaposes BCL2 gene with the light-chain gene on chromosome 2. The presence of BCL2 rearrangement by itself is insufficient for FLs to develop. Additional mutations are required. FISH is more sensitive than PCR in detecting BCL2 rearrangements. About 10-15% of FL cases (pediatric FL, primary cutaneous follicle center lymphoma, and grade 3B FL) lack BCL2 rearrangement.

BCL2 expression is turned off in normal follicle center B cells. In FLs, BCL2 protein is overexpressed (shown in this image) conferring a survival advantage on B cells by preventing apoptosis. BCL2 expression is highest in Grade 1-2 FLs and less frequent in Grade 3 tumors. Expression is BCL2 protein is usually concordant with the presence of BCL2 rearrangements; however, some cases have mutations in the BCL2 gene that cause false-negative result with the commonly used antibody. Therefore, negative BCL2 does not totally rule out follicular lymphoma. Image copyright: pathorama.ch

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