Diffuse large B-cell lymphoma carrying both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32)

We report a 60-year-old man with diffuse large B-cell lymphoma harboring both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32). Although he received six courses of conventional combination chemotherapy plus rituximab, early relapse occurred. Four courses of an intensive salvage regimen and high-dose chemotherapy with autologous peripheral blood stem cell transplantation were performed. The patient has remained in complete remission for over 24 months. This case is noteworthy because both genetic abnormalities are implicated in lymphomagenesis.     

Intravascular large B-cell lymphoma associated with t(14;19)(q32;q13) translocation

We report a 59-year-old man with intravascular large B-cell lymphoma (IVLBCL) associated with hemophagocytic syndrome, disseminated intravascular coagulopathy, and lung involvement. G-banding analysis of the metaphase spreads obtained from the bone marrow showed that the lymphoma cells were near-tetraploid and included two homologues of the 14q+ chromosome. Spectral karyotyping revealed that complex translocations occurred among chromosomes 3, 12, 14, and 19, and additional materials of 14q+ were from chromosome 19 with the breakpoint at 14q32 and 19q13. To the best of our knowledge, this is the first report describing t(14;19)(q32;q13) in IVLBCL.     

Identification of the gene encoding cyclin E1 (CCNE1) as a novel IGH translocation partner in t(14;19)(q32;q12) in diffuse large B-cell lymphoma

In a subset of B-cell malignancies, the genes encoding members of the cyclin D familiy are juxtaposed to immunoglobulin loci through recurrent chromosomal translocations. Here, we identified the gene encoding cyclin E1 as novel translocation partner of the immunoglobulin heavy chain (IGH) locus involved in a t(14;19)(q32;q12) in a case of t(8;14)(q24;q32) IGH-MYC-positive leukemic diffuse large B-cell lymphoma. The translocation breakpoints were cloned and mapped to the switch region Sα1 of IGH in 14q32 and approximately 60kb centromeric to CCNE1 in 19q12. Immunohistochemical analysis revealed overexpression of the cyclin E1 protein in this case, which to a comparable extent was observed in 3/41 independent DLBCL. These data indicate that cyclin E1 may act as a novel oncogene in B-cell lymphomagenesis.     

t(3;22)(q27;q11): a novel translocation associated with diffuse non- Hodgkin's lymphoma [see comments]

Of 187 specimens of non-Hodgkin's lymphoma and four hyperplastic lymphoid proliferations with clonal chromosome abnormalities ascertained serially over a 4 1/2-year period, nine cases with t(3;22)(q27;q11) were identified. Seven of the lymphomas were diffuse tumors, predominantly large cell type. The eighth tumor, a follicular small cleaved cell lymphoma, exhibited a t(3;22) and a t(14;18)(q32;q21). The ninth case was a lymph node from a human immunodeficiency virus-positive patient which showed atypical hyperplasia. Overall survival of t(3;22) diffuse lymphoma patients was not different from that of patients with abnormal karyotypes without t(3;22). The t(3;22) diffuse tumors studied showed a disproportionate frequency of lambda light chain on their cell surfaces, a finding similar to that observed in t(8;22)(q24;q11) Burkitt's lymphomas. Our results indicate that the t(3;22)(q27;q11) is the third most common recurring translocation in diffuse non-Hodgkin's lymphoma.     

Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma

Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of tumours, varying in clinical features, immunophenotype and cytogenetics. The aim of this study was to investigate the prognostic significance of BCL6 gene rearrangement at the 3q27 locus in patients with primary nodal disease, and to examine interrelationships with immunophenotype and International Prognostic Index (IPI). We have developed a fluorescent in situ hybridization (FISH)-based technique for the retrospective analysis of the effect of BCL6 gene rearrangements on survival, using nuclei extracted from paraffin-embedded tissue. FISH results were obtained in 111 presentation cases of nodal DLBCL. The IPI was calculated and each case was stained immunocytochemically for BCL6, BCL2 and CD10. 3q27 rearrangements were detected in 25% of cases. BCL2 protein and a germinal centre (GC) phenotype (defined as CD10+, BCL6+) were expressed in 56% and 41% of cases respectively. In multivariate analysis, rearrangement of 3q27 and BCL2 expression and the absence of a GC phenotype were associated with a poor prognosis. These factors can be used in conjunction with the IPI to improve risk stratification in nodal DLBCL.     

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.     

A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis

We report a novel chromosome translocation--t(2;5)(p23;q35) or its variant, t(2;5;13)(p23;q35;q12)--in 3 patients with peripheral T-cell lymphoma. All 3 were female children who had peripheral lymphadenopathy without organomegaly and underwent complete remission with or without chemotherapy. Their tumors were characterized histologically by predominant large cells, at times showing phagocytosis, and immunologically by peripheral T-cell phenotype and expression of Ki-1 antigen and epithelial membrane antigen (EMA). Since the same translocation has been reported in the literature in 4 patients with malignant histiocytosis (MH), and our patients had histologic features suggestive of that disease, it is likely that many tumors previously interpreted as MH are actually phagocytic large T-cell lymphoma carrying this translocation.     

The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene

Translocations affecting the chromosomal locus 8p12 are hallmarks of an atypical stem cell myeloproliferative disorder. These events disrupt the fibroblast growth factor receptor 1 (FGFR1) gene and fuse the FGFR1 C-terminus catalytic domain with unrelated proteins. Here, we report on the characterization of the 19q13.3 locus as the fifth FGFR1 chromosomal partner.     

Trisomy 12 and t(14;22)(q32;q11) in a patient with B-cell chronic lymphocytic leukemia

Recurrent cytogenetic abnormalities are typically found in about one third of B-cell chronic lymphocytic leukemia patients (B-CLL) by standard cytogenetic analysis and their prognostic relevance is well known. We report a case of a B-CLL patient showing both trisomy 12 and a t(14;22)(q32;q11). Trisomy 12 is often associated with aggressive disease and resistance to chemotherapy, however, our patient is in good health and currently untreated after 7 years, suggesting in this case a relatively good prognosis and a questionable role for translocations involving the 14q32 locus.     

A new translocation t(11;13)(q13;q14) in a mature B-cell neoplasm

We present the case of a man affected by an unclassified mature B-cell neoplasm with a bone marrow culture stimulated with TPA showing a 46,XY, t(11;13)(q13;q14)[14]/46,XY [6] karyotype. Fluorescent in situ hybridization demonstrated that the BCL1 oncogene is translocated (not rearranged) to chromosome band 13q14 and that a copy of D13S319 locus is deleted. To our knowledge, this is the first reported case with this novel cytogenetic aberration.     

Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(11;22)(q13;q11) translocation

Summary The PRAD1 gene identified from the chromosome band 11q13 region was previously demonstrated to be overexpressed in cell lines with t(11:14)(q13;q32) trans-location and was suggested to be a candidate BCL-1 gene. We report here one case of mantle zone lymphoma with a t(11;22)(q13:q11), a variant translocation at the BCL-1 locus, having the PRAD1 overexpression. By analogy with the c-myc gene in Burkitt's lymphoma and the BCL-2 gene in follicular lymphoma, this case supports strongly the idea that the PRAD1 is the candidate BCL-1 gene.