Molecular diagnostic laboratories face such difficulties with the BCL2-IGH translocation in follicular lymphoma and with internal tandem duplication mutation of the FLT3 gene in leukemia, where breakpoints are widely distributed, mutations may be multiple, signal strength is low, and background noise is elevated.
The t(14;18)(q32;q21) involving the IGH and the MALT1 gene has previously been described in PCMZL, whereas the t(14;18)(q32;q21)IGH/BCL2 seems to be restricted to follicular lymphoma and diffuse large B-cell lymphoma.
Intraclonal heterogeneity in follicular lymphoma (FL) is apparent from studies of somatic hypermutation (SHM) caused by activation-induced deaminase (AID) in IGH.
Comparative analysis between RQ-PCR and digital droplet PCR of BCL2/IGH gene rearrangement in the peripheral blood and bone marrow of early stage follicular lymphoma.
Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR).
Although the majority of patients with follicular lymphoma (FL) harbor the t(14;18)(q32;q21)IGH/BCL2 gene rearrangement that leads to the overexpression of BCL2 protein, approximately 20% of FL cases lack t(14;18)(q32;q21).
We performed interphase fluorescence in situ hybridization (FISH) analysis to detect Bcl-2/IgH, Bcl-6 gene rearrangement, Bcl-2 gene amplification, and the cyclinD1/IgH gene in formalin-fixed paraffin embedded specimens from our FL archives.
The sequence analysis of the IgH gene revealed both of cells originated from the same clone, showing that the aggressive BL-like tumor originated from the FL-like clones simultaneously found in the bone marrow.
B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109).
The most common genetic aberration in follicular lymphoma (FL) is the t(14;18)(q32;q21) translocation that juxtaposes the antiapoptotic BCL2 gene with the promoter of the immunoglobulin heavy chain (IgH) gene.
In the present study, 5/6 cases in which FISH was successful had an IGH/BCL2 fusion as would result from the t(14; 18)(q32; q21) translocation commonly seen in FL of extraoral sites.
In the first case, the FLwas negative for IGH-BCL2 and harbored a novel IGH-associated translocation; in the second case, the CL manifested in the skin.
The translocation t(14;18) between the BCL-2 oncogene and the Ig heavy chain (IgH) gene provides the molecular basis for the development of follicular lymphomas.
The FL with signet-ring cell morphology (1/5) tends to lack IGH/BCL2 translocation, and an extended immunohistochemical study is recommended for correct diagnosis and classification of SRCL.
Translocation t(14;18)(q32;q21) and/or BCL-2-IGH gene rearrangements were the genomic alterations most frequently observed: 50% of S-DLBCL and 30% of dn-DLBCL.
Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone.
This study aimed to determine the correlations of 7 histopathologic prognostic indicators of follicular lymphoma (follicular lymphoma grade, CD10 expression, Bcl-2 expression, IGH/BCL2 fusion, diffuse area, fibrosis, and marginal zone differentiation) with progression-free survival, overall survival, and follicular lymphoma histologic grade in 255 follicular lymphoma patients who were treated with rituximab-containing therapy.
Polymerase chain reaction (PCR) amplification, cloning, and sequencing of the junctional region of the hybrid bcl-2/IgH genes showed identical nucleotide sequences in multiple biopsy specimens of FL that did not show morphologic transformation.
In conclusion, pretreatment quantity of BCL2/IGH in PB or BM seems to mirror the extent of disease and can provide an auxiliary prognostic parameter in FL.
Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking).
We studied 8 patients with both FL and H/DC neoplasms using immunohistochemistry, fluorescence in situ hybridization (FISH) for t(14;18), and polymerase chain reaction (PCR)/sequencing of BCL2 and IGH rearrangements.