The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( Â 1), gastric MALT lymphoma ( Â 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( Â 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.
Chromosomal translocations affecting the immunoglobulin loci, particularly immunoglobulin heavy chain (IGH) genes complex at 14q32, are a hallmark of B cell malignancies.1,2 They usually result in deregulated expression of involved oncogenes (eg, BCL1, CMYC, and PAX5) juxtaposed to the regulatory elements of IGH. As some of these translocations are associated with specific subtypes of mature B cell lymphoma and have prognostic significance, their detection is of clinical importance. In daily practice, IGH translocations have been routinely analyzed by fluorescence in situ hybridization (FISH) using either a common LSI IGH dual-color, break-apart rearrangement assay or dual-color, dual-fusion oncogene-specific probe, such as LSI IGH/CCND1, IGH/ BCL2, and IGH/CMYC.The IGH-mediated translocations are relatively rare in B cell chronic lymphocytic leukemia (CLL), [3][4][5] which is the most common form of leukemia in adults and shows a highly variable clinical course. The CLL cells display a phenotype of mature activated B lymphocytes expressing CD19, CD5, and CD23 and having reduced levels of membrane IgM, IgD, and CD79b. The co-expression of CD19 and CD5, however, is also characteristic for mantle cell lymphoma (MCL), which, in contrast to CLL, is usually an aggressive disease hallmarked by the t(11;14)(q13; q32)/IGH-CCND1 rearrangement. Differential diagnosis between CLL and leukemic MCL is sometimes challenging. 5 Given that up to 30% of MCL cases have immunophenotypic features characteristic of B-CLL, albeit usually with atypical, pleomorphic morphology, 6 immunophenotyping alone is insufficient to exclude a diagnosis of MCL. Therefore, in the Belfast City Hospital (Belfast, Northern Ireland) all suspected CLL cases have been routinely examined by rapid interphase FISH with the LSI IGH/CCND1 assay to identify t(11;14)-positive MCL cases, in addition to examination for CLL typical cytogenetic aberrations. During this analysis, a subset of CLL
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