t(11;18)(q21;q21.1): A recurring translocation in lymphomas of mucosa-associated lymphoid tissue (malt)?

A distinct subtype of extranodal malignant lymphoma derived from mucosa-associated lymphoid tissues (MALT) has recently been defined. We have detected an acquired t(11;18)(q21;q21.1) in a patient with a MALT lymphoma of the stomach. This translocation has previously been described in two other patients with extranodal lymphoma. The BCL2 oncogene, which is located at band 18q21.3 and is activated by the t(14;18)(q32;q21) in follicular lymphoma, was not rearranged in this case. This newly identified t(11;18) may be a recurring translocation specifically associated with MALT lymphomas. Genes located at the breakpoint sites of chromosome 11 and/or chromosome 18 may be crucial to the pathogenesis of this type of malignant lymphoma.     

t(11;18)染色体易位对于胃黏膜相关淋巴组织淋巴瘤的预后价值

目的 探讨t(11;18)(q21;q21)染色体易位对于胃黏膜相关淋巴组织(mucosal associated lymphoid tissue,MALT)淋巴瘤预后意义.方法 采用回顾性方法对1994年1月至2004年6月间,经术后病理明确诊断的36例MALT淋巴瘤患者进行随访,同时采用间期荧光原位杂交技术检测患者保存的石蜡手术标本有无t(11;18)(q21;q21)染色体易位.结果 36例患者中15例检出t(11;18)(q21;q21)染色体易位,阳性率为41.67％;35例随访至2010年3月,总的中位生存期87个月,伴有t(11;18)(q21;q21)染色体易位者的中位生存期为43个月,无t(11;18)(q21;q21)染色体易位者的中位生存期为130个月,两组之间差异有统计学意义(x2 =29.57,P＜0.01).结论 t(11;18)(q21;q21)染色体易位是MALT淋巴瘤的重要预后因素.     

The B‐cell‐activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa‐associated lymphoid tissue lymphoma without t(11;18)(q21;q21)

We previously reported that activation of the B‐cell‐activating factor (BAFF) pathway upregulates nuclear factor‐κB (NF‐κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)‐independent gastric diffuse large B‐cell lymphoma (DLBCL) tumours with evidence of mucosa‐associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low‐grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty‐four patients who underwent successful HP eradication for localized HP‐positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP‐independent group than in the HP‐dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF‐R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF‐κB (p65) (p = 0.001) and NF‐κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF‐R expression and nuclear BCL3, BCL10, NF‐κB (p65) and NF‐κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP‐dependent cases and 18 HP‐independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)‐negative lymphoma cells was further studied in two types of lymphoma B cell: OCI‐Ly3 [non‐germinal centre B‐cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA‐1 [t(14;18)(q32;q21)/IGH‐MALT1‐positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF‐κB and AKT pathways, and induced the formation of BCL10–BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF‐κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non‐canonical NF‐κB pathways (p52) through tumour necrosis factor receptor‐associated factor 3 degradation, NF‐κB‐inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF‐κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Primary macroglobulinemia with t(11;18)(q21;q21)

These are the first cases of primary macroglobulinemia (PMG) with t(11;18)(q21;q21) reported in the literature. The first case was a 77-year-old man with macroglobulinemia (serum IgM: 8.36 g/dL). Abnormal lymphoid cells were detected in the blood and bone marrow. Immunologic and karyotypic analyses revealed that abnormal cells were positive for surface IgM-k, CD19, and CD20, negative for CD5 and CD10, and all had a t(11;18)(q21;q21). The second case was a 57-year-old woman with macroglobulinemia (serum IgM: 12.0 g/dL). Abnormal lymphoid cells were detected in blood and marrow, and cells were positive for surface IgM-lambda, CD19, and CD20, and negative for CD5 and CD10. Plasma cells bearing cytoplasmic IgM-lambda were increased in pleural fluid. Karyotyping demonstrated t(2;11;18)(q21-23;q21;q21). Rearrangements within BCL2 and YES genes located at 18q21 were not detected. Sixteen other cases with t(11;18)(q21;q21) have been reported in marginal zone B-cell lymphoma. Therefore, our report is in agreement with the finding that part of primary macroglobulinemia is a variant of marginal zone B-cell lymphoma.     

Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization

A chromosomal t(11;18)(q21;q21) recurrently found in marginal zone lymphomas of mucosa-associated lymphocytic tissue (MALT) type is one of the key determinants of their treatment and outcome because t(11;18)-positive cases are resistant to Helicobacter pylori eradication therapy. To detect t(11;18) on paraffin-embedded tissue sections, we established a method of dual-color fluorescence in situ hybridization (D-FISH) using DNA probes directly labeled with SpectrumGreen and SpectrumOrange (tissue-FISH [T-FISH]). T-FISH detected the t(11;18) as colocalized signals between the band-specific yeast artificial chromosome (YAC) clones y966e4 (11q21) and y943b8 (18q21) on the der(11)t(11;18). The t(11;18) was detected in four of 22 patients with marginal zone lymphoma of MALT type in 72%-78% of the cells. In both patients studied, the percentage of t(11;18)-positive cells was much higher in tissue-FISH analysis than in interphase-FISH: 74% versus 30% in patient 1 and 75% versus 31% in patient 4. None of the 12 patients with diffuse large B-cell lymphoma of the stomach showed the t(11;18). Tissue-FISH is a powerful tool for the diagnosis of marginal zone lymphoma of MALT type because it can be applied not only to small specimens obtained from endoscopic biopsy samples but also to archival materials, hence facilitating the delineation of subtypes in marginal zone lymphoma of MALT type.     

t（11;18）（q11;q23）一家系

先证者　男 ,30岁 ,表型正常。婚后 3年 ,其妻怀孕 5次 ,均在孕 2～ 3个月自然流产 ,妇科检查正常。夫妇非近亲结婚。患者外生殖器正常。精液检查精子数量正常。细胞遗传学检查 :外周血细胞染色体观察 ,常规外周血淋巴细胞培养 ,G显带分析30个细胞 ,先证者核型为 46 ,XY,t(11;18) (11pter→ 11q11∷18q2 3→ 18qter;18pter→ 18q2 3∷ 11q11→ 11qter) ,其妻染色体核型正常。先证者性细胞联会复合体 (synaptonemal complex,SC)观察 ,方法参照文献 [1]。睾丸活检微铺展的 SC电镜观察 ,分析 30个精母细胞 (从早粗线期到晚粗线期 )中 SC图…     

Clinical, morphologic, and cytogenetic characteristics of patients with lymphoid malignancies characterized by both t(14;18)(q32;q21) and t(8;14)(q24;q32) or t(8;22)(q24;q11)

Six patients with an aggressive leukemia/lymphoma disorder had a t(14;18) as well as either a t(8;14) (three patients) or a t(8;22) (three patients). Leukemia cells from all three patients with the t(8;22) had a mature B cell phenotype (Smlg + and TdT-), whereas two of three patients with the t(8;14) had a pre-B phenotype and were Smlg-. None of the patients with the t(8;22) had a prior history of follicular lymphoma, whereas two of the three patients with the t(8;14) had had a follicular lymphoma. The clinical, cytogenetic, and morphologic characteristics of these six patients along with eight previously reported cases with both the t(14;18) and the t(8;14), the t(8;22) or the t(2;8) are discussed.     

t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma.

We have identified two cases of previously untreated, small lymphocytic lymphoma with extranodal involvement, which had a reciprocal translocation, t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are remarkably similar to two previously reported cases carrying this translocation with regard to clinical features, cytogenetic abnormality, histologic subtype, and immunophenotype. Molecular genetic analysis of these two cases revealed clonal gene rearrangement of the IGH locus but only germline configuration of the BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2 rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement appear to make up a phenotypically identifiable subgroup. Identification of the genes at the translocation breakpoints will be important.     

Chromosome 18 breakpoint in t(11;18)(q21;q21) translocation associated with MALT lymphoma is proximal to BCL2 and distal to DCC

The t(11;18)(q21;q21) translocation has recently been identified as a recurring chromosomal abnormality in a subset of extranodal marginal zone B‐cell lymphoma, a low‐grade lymphoma of mucosa‐associated lymphoid tissue (MALT). Neither the 11q21 nor the 18q21 breakpoints have been characterized by molecular genetic analysis. As a prelude to isolation of the gene(s) involved in this translocation, we have mapped the 18q21 breakpoint region by fluorescence in situ hybridization (FISH) of YAC and PAC clones. We mapped 37 YACs assigned to a 29‐cM region within the chromosomal band 18q21. Using nine of these YACs in single‐ and/or dual‐color FISH to analyze three cases of MALT lymphomas with the t(11;18)(q21;q21) translocation, we localized the breakpoints within a 1.6‐Mb nonchimeric YAC (938E1). This YAC is useful for the detection of the translocation in metaphase and in interphase cells. A nonchimeric YAC contig of an 8‐cM region around the breakpoint comprising nine YACs and a PAC contig of YAC 938E1 were constructed, which enabled the refinement of the breakpoint region in the proximal region of the YAC within a <820‐kb segment. This breakpoint is proximal to the BCL2 locus and distal to DCC and DPC4 loci in chromosomal band 18q21. Genes Chromosomes Cancer 24:156–159, 1999. © 1999 Wiley‐Liss, Inc.     

染色体46,XY,t(18;21)(q11;q22)平衡易位携带者一例

目的报道染色体46,XY,t(18;21)(q11;q22)平衡易位携带者1例。方法采用外周血淋巴细胞培养法,G显带。结果染色体核型分析为46,XY,t(18;21)(q11;q22)。结论平衡易位是导致不良孕产的重要原因,也是导致男性不育的常见原因。如查出平衡易位携带者,给予他们正确的优生指导及产前诊断,对降低出生缺陷的发病率有重要的作用。     

t(11;18)(q21;q21) may delineate a spectrum of diffuse small B-cell lymphoma with extranodal involvement

We describe a patient with stage IV non-Hodgkin's lymphoma (NHL) and a t(11;18)(q21;q21) translocation. He presented with a gastric small B-cell lymphocytic lymphoma, expressing IgAL immunoglobulins without expression of CD10, CD5, and CD23 antigens. The lymphoma was the final development of a 6-year history of a monoclonal IgAL increase complicated by severe renal failure due to membranoproliferative glomerulonephritis. The clinical, histological, immunologic, and cytogenetic features of this patient are very similar to those observed in the five other patients with t(11;18) reported to date. This translocation therefore seems to delineate a new subtype of diffuse small B-cell lymphoma with involvement of mucosal sites. Involvement of the BCL2 oncogene on 18q21 could not be detected using molecular techniques with 5′ as well as 3′ BCL2 probes, indicating that other, so far unknown, genes relevant to lymphoid differentiation could be located in 18q21 and 11q21. © 1993 Wiley-Liss, Inc.     

t(1;18)(q32.1;q22.1) associated with genitourinary malformations

We report a male infant who has impaired penile development, hypospadias, and mild developmental delay with a 46,XY,t(1;18)(q32.1;q22.1) karyotype. Fluorescent in situ hybridization (FISH) was performed to more precisely map the translocation breakpoint. The translocation breakpoint maps to a region that has been implicated in genitourinary malformations in the 18q- syndrome. This case report suggests that a gene involved in genitourinary development maps at or near the chromosome 18 translocation breakpoint.     

Translocation t(11;14)(q13;q32) in chronic lymphoid disorders.

The translocation t(11;14)(q13;q32) has been described in a spectrum of B-lymphoproliferative diseases and involves a putative oncogene, BCL1, which maps to chromosome band 11q13. Recent evidence indicates that this abnormality may delineate particular subtypes of lymphoma, such as intermediate lymphocytic and centrocytic lymphomas. Thus the possible significance of the t(11;14) within B-cell disorders should be reexamined in the light of a more objective approach to classifying these diseases by morphology, histology, and immunophenotype. We describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with chronic lymphoid disorders in whom clonal chromosome abnormalities were detected. All the cases were leukemic: prolymphocytic (B-PLL; 4/15 cases), chronic lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non-Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and follicular (1 case). None of the CLL (25) or hairy cell leukemia cases (15) had t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B cells with lymphoplasmacytic features as judged by morphology and immunophenotype.     

Acute myeloid leukemia with t(5;18)(q35;q21).

A case of acute myelocytic leukemia with a translocation (5;18)(q35;q21) is reported. Cytogenetic abnormalities of the long arm of chromosome 5 have long been known to affect hematopoiesis. Although translocations between 5q and other chromosomes have been associated with malignancy, this is the first reported case of a t(5;18) resulting in acute myeloid leukemia. Possible molecular mechanisms underlying the pathogenesis of the disease are discussed.     

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley-Liss, Inc.