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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The t(11;18)(q21;q21) is thought to represent an important primary event in the development of marginal zone lymphomas, although an accurate estimation of the frequency and distribution of this genetic alteration among nodal, splenic, and extranodal marginal zone lymphoma types has yet to be determined. Recently, molecular genetic studies have shown that this translocation results in the fusion of the API2 gene on chromosome 11 and a novel gene termed MALT1 on chromosome 18. To investigate the incidence of API2-MALT1 fusion transcripts among marginal zone lymphomas and to determine possible marginal zone lymphoma subtype associations, we used reverse transcriptase-polymerase chain reaction to analyze RNAs extracted from frozen tissue samples of 99 marginal zone lymphomas. Fifty-seven involved diverse extranodal sites including 14 stomach, 11 lung, 7 orbit, 7 parotid, 5 thyroid, 5 lacrimal gland, 3 small intestine, 2 large intestine, 1 kidney, 1 paraspinal region and 1 skin. Twenty-one primary splenic and twenty-one primary nodal marginal zone lymphomas were also studied. API2-MALT1 fusion transcripts were detected in 12 of 57 extranodal marginal zone lymphomas (21%), but in none of the nodal or splenic cases. The cDNA sequences of the fusion transcripts were determined, revealing variation in the coding sequence fusion point for both API2 and MALT1. The findings suggest that t(11;18)(q21;q21) is restricted to extranodal marginal zone lymphomas and that these tumors have distinct genetic etiologies in comparison with their splenic and nodal counterparts.
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PMID:Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. 1075 43

The translocation of chromosome 11, long arm, region 2, band 1, to chromosome 18, long arm, region 2, band 1 (t(11;18)(q21;q21)) represents a recurrent chromosomal abnormality in extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (MALT) type and leads to a fusion of the apoptosis inhibitor-2 (API2) gene on chromosome 11 and the MALT lymphoma-associated translocation (MLT) gene on chromosome 18. A 2-color fluorescence in situ hybridization (FISH) assay, which can be used for the detection of t(11;18) in interphase nuclei and metaphase chromosomes on fresh and archival tumor tissue, was developed. The P1 artificial chromosome (PAC) clone located immediately telomeric to the MLT gene and the PAC clone spanning the API2 gene were differentially labeled and used to visualize the derivative chromosome 11 resulting from t(11;18), as evident by the overlapping or juxtaposed red and green fluorescent signals. The assay was applied to interphase nuclei of 20 cases with nonmalignant conditions and 122 B-cell non-Hodgkin's lymphomas (NHLs). The latter group comprised 20 cases of nodal follicle center cell lymphoma and diffuse large B-cell NHL, 10 cases of gastric diffuse large B-cell lymphoma, 10 cases of hairy cell leukemia, and 82 cases of MZBCL (41 extranodal from various locations, 19 nodal, and 22 splenic MZBCL) including 35 cases with an abnormal karyotype, 2 of which revealed t(11;18). By interphase FISH, t(11;18) was detected in 8 gastrointestinal low-grade MALT-type lymphomas including the 2 cytogenetically t(11;18)(+) cases. In the 8 t(11;18)(+) cases, the FISH results were confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) using API2 and MLT specific primers. Our results indicate that t(11;18)(q21;q21) specifically characterizes a subgroup of low-grade MZBCL of the MALT-type and that the FISH assay described here is a highly specific and rapid test for the detection of this translocation.
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PMID:Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. 1097 68

Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) represent a distinct clinicopathological entity that arises in a wide variety of extranodal sites. Genetically, MALT lymphomas are characterized by the t(11;18)(q21;q21). The genes involved in this translocation have been identified to be API2 on chromosome 11, which encodes an apoptotic inhibitor, and MALT1, a novel gene on chromosome 18. We identified the t(11;18)(q21;q21) by Southern blot analysis and reverse transcriptase PCR in 42% of a panel of extranodal MALT lymphomas. We also identified the breakpoints within the API2 and MALT1 genes in 7 patients, which revealed a consistent breakpoint after the third baculoviral inhibitor of apoptosis repeat domain within API2, and variable breakpoints in MALT1. We determined the API2/MALT1 fusion transcript in 2 cases by Northern blot analysis and also showed that MALT1 mRNA is constitutively expressed in a variety of human tissues. To understand the functional consequence of the translocation, we determined the pattern of expression of API2 and MALT1 through B lineage differentiation. API2 was expressed only in cell lines which correspond to mature B cells, whereas MALT1 mRNA was detectable in pre-B cells, mature B cells and plasma cells. These results suggest that fusion of MALT1 to API2 mediated by the t(11;18)(q21;q21) may result in an increased inhibition of germinal center B cell apoptosis and subsequent development of MALT lymphomas.
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PMID:The API2/MALT1 fusion product may lead to germinal center B cell lymphomas by suppression of apoptosis. 1109 64

Malignant lymphoma of mucosa-associated lymphoid tissue (MALT) type is a distinct clinicopathological disease entity in the category of extranodal marginal zone B-cell lymphoma. Recently, we and others have shown that the API2 gene on chromosome 11 and the MALT1 gene on chromosome 18 are fused as a result of t(11;18)(q21;q21) in MALT lymphomas. Here we report a detection assay that can be used for formalin-fixed, paraffin-embedded specimens. It consists of a multiplex one-tube reverse transcriptase-polymerase chain reaction (RT-PCR) followed by three parallel multiplex nested polymerase chain reactions. Eight variants of the fusion transcripts have been reported to date. When these variants were used as positive controls, all were successfully detected. The subsequent direct sequencing confirmed the results. Using this rapid and simple method, we could detect API2-MALT1 fusion transcripts in 5 of 15 (33%) archival cases of MALT lymphoma for a frequency comparable with those of RT-PCR assays using frozen materials. The lung was the preferential anatomical site of origin of MALT lymphomas harboring API2-MALT1 fusion. No fusion transcript was detected in any of 20 high-grade B-cell lymphomas. Our multiplex RT-PCR assay, which can be used for routinely-processed paraffin samples, should serve as a useful molecular tool for clarifying the clinicopathological significance of API2-MALT1 fusion in MALT lymphoma.
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PMID:API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma: multiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens. 1115 7

T(11;18)(q21;q21) is the most common structural abnormality in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) leading to the fusion of the apoptosis inhibitor-2 (API2) gene and the MALT lymphoma-associated translocation (MALT1) gene. In 2 patients with MALT lymphoma of the liver and skin, respectively, t(14;18)(q32;q21) was observed by cytogenetic analysis. Subsequent fluorescence in situ hybridization (FISH) studies disclosed that the immunoglobulin heavy-chain locus (IGH) and the MALT1 gene were rearranged by this translocation. In order to screen a large series of MALT lymphomas for this aberration, a 2-color interphase FISH assay was established. Among a total of 66 cases, t(14;18)(q32;q21) involving IGH and MALT1 was detected in MALT lymphomas of the liver (4 of 4), skin (3 of 11), ocular adnexa (3 of 8), and salivary gland (2 of 11), but did not occur in MALT lymphomas of the stomach (n = 10), intestine (n = 9), lung (n = 7), thyroid (n = 4), or breast (n = 2). In total, 12 of 66 (18%) MALT lymphomas harbored t(14;18)(q32;q21); 7 additional cases of splenic marginal zone lymphoma tested negative. All of the 12 MALT lymphomas featuring the t(14;18)(q32;q21) were negative for t(11;18)(q21;q21) by reverse transcriptase-polymerase chain reaction (RT-PCR). However, trisomy 3 and/or 18 was found in 4 of 12 cases, suggesting that the t(14;18)(q32;q21) does not occur as the sole genetic abnormality. This study identifies IGH as a new translocation partner of MALT1 in MALT lymphomas, which tend to arise frequently at sites other than the gastrointestinal tract and lung. In contrast to t(11;18)(q21;q21)(+) MALT lymphomas, those with t(14;18)(q32;q21) may harbor additional genetic abnormalities.
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PMID:T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. 1240 90

The chromosomal translocation t(11;18) is a unique chromosomal aberration associated with mucosa-associated lymphoid tissue lymphoma. API2 and MALT1 genes have been identified around this translocation. We attempted to find chromosomal abnormalities focusing mainly on the t(11;18) translocation in formalin-fixed, paraffin-embedded tissues of ocular adnexal lymphoproliferative disorders using multiplex reverse transcriptase-polymerase chain reaction and/or two-color interphase fluorescence in situ hybridization. By these methods, the t(11;18) translocation was detected in 1 of 8 patients with reactive lymphoid hyperplasia (13%), 3 of 23 with mucosa-associated lymphoid tissue lymphoma (13%), and 2 of 14 with diffuse large B-cell lymphoma with/without mucosa-associated lymphoid tissue lymphoma (14%). Moreover, we performed fluorescence in situ hybridization analysis to detect any numerical aberration of chromosomes 3, 7, 12, and 18 on some specimens nonselectively. No numerical chromosomal abnormalities were detected in 3 cases of reactive lymphoid hyperplasia, whereas three of four cases of mucosa-associated lymphoid tissue lymphoma and all four cases of diffuse large B-cell lymphoma with/without mucosa-associated lymphoid tissue lymphoma components exhibited one or more abnormalities. These findings indicate a possibility that at least in the ocular adnexa, some diffuse large B-cell lymphomas are derived from mucosa-associated lymphoid tissue lymphomas.
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PMID:Involvement of the chromosomal translocation t(11;18) in some mucosa-associated lymphoid tissue lymphomas and diffuse large B-cell lymphomas of the ocular adnexa: evidence from multiplex reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization on using formalin-fixed, paraffin-embedded specimens. 1274 51

In the present study, 62 cases of ocular adnexal lymphoproliferative disorders were reviewed clinicopathologically. Of them, 51 were extranodal marginal zone B-cell lymphoma (MALT lymphoma), five were diffuse large B-cell lymphoma (DLBCL), one was peripheral T-cell lymphoma, one was NK/T cell lymphoma, nasal type, and four were reactive lymphoid hyperplasia. These lymphoma cases showed a favorable clinical course and localized disease, except for the case of NK/T cell lymphoma, although 19 cases (32.8%) had a recurrence of disease. To clarify the correlation between BCL10 protein expression and API2-MALT1 gene rearrangement, the 51 cases of MALT lymphoma and 5 cases of DLBCL were analyzed by immunohistochemical and RT-PCR methods. Nuclear BCL10 expression was identified in 58% of MALT lymphoma cases, but not in any DLBCL cases. There was no evidence of a correlation between aberrant nuclear BCL10 expression and the clinical parameters examined in the present study. API2-MALT1 transcription was not demonstrated in either the MALT lymphoma cases or the DLBCL cases studied using a multiplex one-tube reverse transcriptase-PCR method. These findings indicate that the nuclear expression of BCL10 is unlikely to correlate with the API2-MALT1 fusion gene in ocular adnexal MALT lymphoma.
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PMID:No evidence of a correlation between BCL10 expression and API2-MALT1 gene rearrangement in ocular adnexal MALT lymphoma. 1467 90

Inhibition of apoptosis seems to play an important role in the pathogenesis of marginal zone lymphoma. Apoptosis regulator B-cell lymphoma 10 (BCL10) may show aberrant nuclear localization in some aggressive extracutaneous MALT lymphomas, often in association with a MALT1 gene t(11;18)(q21;q21) translocation. The possible occurrence of this association in primary cutaneous marginal zone lymphoma (PCMZL) remains insufficiently explored. The aim of this study was to evaluate BCL10 protein expression pattern and its possible relationship to the presence of t(11;18)(q21;q21) and other MALT1 gene abnormalities in PCMZL and to assess their clinical significance. The study included 42 consecutive PCMZL patients diagnosed on the basis of the World Health Organization/European Organization for the Research and Treatment of Cancer classification criteria. BCL10 expression was immunohistochemically evaluated in all cases, whereas t(11;18)(q21;q21) reverse transcriptase polymerase chain reaction amplification was performed on 21 samples. In addition, the presence of other MALT1 gene translocations was explored in 26 samples by interphase fluorescence in situ hybridization using a MALT1 locus-specific probe. We observed the presence of aberrant nuclear BCL10 expression in a significant number of PCMZL cases (36%, 15/42). This aberrant expression was significantly related to the development of extracutaneous disease. In contrast, neither the t(11;18)(q21;q21) translocation nor other MALT1 gene translocations could be demonstrated. t(11;18)(q21;q21), strongly linked to extracutaneous MALT lymphomas, does not seem to play a role in PCMZL. The participation of other MALT1 gene translocations in PCMZL pathogenesis seems also unlikely.
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PMID:Aberrant nuclear BCL10 expression and lack of t(11;18)(q21;q21) in primary cutaneous marginal zone B-cell lymphoma. 1678 87

Pancreatic cancer (PanCa) is characterized by perineural invasion (PNI), early lymph node and liver metastasis, and poor prognosis. PNI is one of the important causes of local recurrence. Little is known about the mechanism of PNI in PanCa. We presented a novel model system that may shed light on the mystery of PNI in PanCa. In this study, mouse dorsal root ganglia (DRGs) and human PanCa cell line (MIA PaCa-2) were cocultured in Matrigel matrix (BD Biosciences, San Jose, CA) to build this PNI model. MIA PaCa-2 cell line alone (control 1) or DRG alone (control 2) was cultured with Matrigel matrix as controls. Neurite outgrowth, cell colony growth, neurite-colony contact, and retrograde extension were observed under inverted microscopy and then were photographed and quantitated with the Optimas imaging system (Optimas Corp., Bothell, MA). At day 14, both the experimental and control 2 samples were harvested and subjected to total RNA isolation and fixed in paraffin-embedded blocks. Slides cut from paraffin blocks were studied with Ki-67 immunostaining and TUNEL assay. Gene profiling was performed using complementary DNA microarray. Overexpressed target genes were verified by quantitative reverse transcriptase polymerase chain reaction. The results showed that reciprocity was observed between neurites and MIA PaCa colonies with 24 hours of coculture. Neurite outgrowth was stimulated in the presence of pancreatic carcinoma cells, which showed 2-fold more area than did control 2. After 72 hours, MIA PaCa colonies cocultured with DRG exhibited 58% more colony area than did control 1. The Ki-67 index of the DRG/MIA PaCa cells (mean, 5.02%) was significantly higher than that in control 1 (mean, 1.18%) (P < .05); in contrast, the apoptotic index in the DRG/MIA PaCa cells was significantly lower (mean, 0.45%) than that in the control 1 (mean, 1.85%) (P < .001). Prosurvival genes MALT1 and TRAF were increased 2-fold in DRG/MIA PaCa compared with controls. We demonstrated that neural-epithelial interaction is a mutually beneficial process for the growth of nerves and PanCa cells. It is possible that oncogenes and growth factors might act synergistically in promoting proliferation and/or inhibiting apoptosis, a survival strategy crucial to the development of PNI in PanCa.
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PMID:Enhanced survival in perineural invasion of pancreatic cancer: an in vitro approach. 1709 19

So far, only one variant translocation of the t(11;18)(q21;q21), the t(11;12;18) (q21;q13;q21), has been reported. We herein describe two new variant translocations, the t(6;18;11)(q24;q21;q21) and the t(11;14;18)(q21;q32;q21), occurring in mucosa-associated lymphoid tissue (MALT) lymphomas. In both cases, fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of an 5'API2-3'MALT1 fusion product, encoded on the derivative chromosome 11. Exon 7 of API2 was fused with exon 5 of MALT1 in the t(11;14;18) and with exon 8 of MALT1 in the t(6;18;11). FISH revealed the involvement of the immunoglobulin locus in the t(11;14;18). Rapid amplification of cDNA ends (RACE)-PCR to detect the involved partner gene on 6q showed exclusively wild-type API2 and MALT1 sequences.
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PMID:The translocations t(6;18;11)(q24;q21;q21) and t(11;14;18)(q21;q32;q21) lead to a fusion of the API2 and MALT1 genes and occur in MALT lymphomas. 1733 92


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