Molecular subtyping of gastric MALT lymphomas: implications for prognosis and management

Du, Min; Atherton, JC

doi:10.1136/gut.2004.061663

Cited by 69 publications

(53 citation statements)

References 84 publications

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“…This is also consistent with the clinical response of gastric MALT lymphoma to H. pylori eradication therapy. Although most of t(11;18)-positive gastric MALT lymphomas do not respond to H. pylori eradication, there are occasional cases responsive to the antibiotic treatment, 37 suggesting that not all translocations have the same biological effect. Equally, the majority of translocation-negative gastric MALT lymphomas can be cured by H. pylori eradication, but there are 10-20% cases that are negative for MALT1, BCL10 and FOXP1 involved translocations, and do not respond to H. pylori eradication, 37 suggesting presence of other unknown genetic abnormalities that may also target the NF-kB pathway.…”

Section: Molecular Mechanism Of Translocation-positive Malt Lymphomamentioning

confidence: 99%

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Hamoudi

Appert

et al. 2010

Leukemia

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Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/ BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-jB pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-jB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-jB target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/lymphoma (BCL)2, while translocationnegative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-jB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.

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Section: Molecular Mechanism Of Translocation-positive Malt Lymphomamentioning

confidence: 99%

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Hamoudi

Appert

et al. 2010

Leukemia

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“…[1][2][3][4][5] Gastric B-cell lymphomas usually exhibit chromosomal translocations involving IGH. [14][15][16] Molecular cloning of IGH translocation breakpoints has been successfully used to identify novel cancerrelated genes in B-cell lymphomas. 17,18 In this study, we used inverse polymerase chain reaction (PCR) 18 to identify a novel translocation involving the 5Ј S region of the IGH gene (IGHS) and CD44 (located at chromosome 11p13) in gastric as well as other mature B-cell NHLs.…”

Section: Introductionmentioning

confidence: 99%

CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation

Chen

Liang

et al. 2010

Blood

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Using inverse polymerase chain reaction, we identified CD44, located on chromosome 11p13, as a novel translocation partner of IGH in 9 of 114 cases of gastric, nongastric extranodal, follicular, and nodal diffuse large B-cell lymphoma (DLBCL). Notably, these translocations involving IGHS were detected in follicular lymphomas and exclusively in germinal center IntroductionMature B-cell non-Hodgkin lymphomas (NHLs) are often associated with chromosomal translocations involving IGH at chromosome band 14q32. 1-5 V(D)J rearrangement and class switch recombination (CSR) are IG rearrangement processes that occur during B-cell development. [6][7][8][9] In CSR, DNA breakage is mediated by activation-induced cytidine deaminase in the germinal centers (GCs) of secondary follicles. 10,11 Any aberrant rearrangement during the DNA breakage and repair processes composed of V(D)J rearrangement and CSR may consequently generate a chromosomal translocation. 12,13 IGH translocations contribute to the pathogenesis of B-cell lymphomas via deregulated expression of the genes located at the partner chromosome locus partly because of the presence of potent B cell-specific transcriptional enhancers within the IGH gene locus. [1][2][3][4][5] Gastric B-cell lymphomas usually exhibit chromosomal translocations involving IGH. 14-16 Molecular cloning of IGH translocation breakpoints has been successfully used to identify novel cancerrelated genes in B-cell lymphomas. 17,18 In this study, we used inverse polymerase chain reaction (PCR) 18 to identify a novel translocation involving the 5Ј S region of the IGH gene (IGHS) and CD44 (located at chromosome 11p13) in gastric as well as other mature B-cell NHLs. Functional studies suggest a possible pathogenic role of this IGHS/CD44 translocation in mature B-cell malignancies. Methods Detection of translocations involving the IGHS by inverse PCRGenomic DNA extracted from frozen sections of tumor specimens from gastric 19 and other mature B-cell NHL cases (supplemental Table 1, available on the Blood website; see the Supplemental Materials link at the top of the online article) was digested with HindIII, and long-distance inverse PCR was performed to detect translocations involving the IGHS region using the primers SAE/JXE, followed by SAI/JXI 18 (supplemental Table 2). Overexpression of CD44⌬Ex1-GFP tagged protein in transfected BJAB cellsCD44⌬Ex1 (CD44 variant mRNA lacking exon 1) and CD44s (standard form; wild-type) cDNAs were amplified by reverse-transcribed (RT)-PCR (supplemental Table 2) from total RNA extracted from a case of gastric lymphoma with the IGHS/CD44 translocation (GL47) and from the peripheral blood lymphocytes of a healthy volunteer; they were then cloned For personal use only. on April 29, 2019. by guest www.bloodjournal.org From in-frame with green fluorescent protein (GFP) at the C-terminus of the pmaxFP-Green-N vector (Amaxa) and transfected into the CD44 Ϫ GC B cell-like (GCB)-diffuse large B-cell lymphoma (DLBCL) cell line BJAB by nucleofection (Amaxa). The subcellular loca...

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“…16 Another translocation involving MALT1, t(14;18)(q32;q21) IGH-MALT1, which is frequent in pulmonary or ocular type MALT lymphomas, are rarely observed in gastric MALT lymphomas. 2,20 The clinicopathologic relationship of this translocation in gastric MALT lymphoma was not well known.…”

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Clinicopathologic Study of Chromosomal Aberrations in Gastric Lymphomas of Korean Patients

Kim

et al. 2009

Korean J Pathol

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Gastric extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) is a unique entity in that pathogenetic role of a microbial agent, Helicobacter pylori (H. pylori) is well established. 1 Chronic antigenic stimulation by H. pylori causes proliferation of lymphoid tissue that is originally absent in normal gastric mucosa, and furthermore promotes the development of low grade malignant lymphoma by acquisition of genetic aberrations such as balanced translocations. The known balanced translocations in MALT lymphomas include t(11;18) (q21;q21) API2-MALT1, t(14;18)(q32;q21) IgH-MALT1, t(1; 14)(p22;q32) BCL10-IgH, and t(3;14)(p14.1; q32) FOXP1-IgH.2 Among these four types of translocation, t(11;18)(q21;q21) harboring API2-MALT1 fusion is the most common chromosomal aberration reported in gastric MALT lymphoma. 3There have been various studies about the incidence of translocation in gastric MALT lymphoma, which were described mainly from Western and Japanese countries. According to the published data, t(11;18) translocation was found in 5-48% of the cases in previous studies. [4][5][6][7][8][9][10][11][12][13][14][15][16] In a recent collective study, Remstein et al.suggested geographic variation might be present in the incidence of translocation in gastric MALT lymphoma, comparing the published data about the incidence of translocation between Europe, Japan and North America. 15 In contrast, there was a new, conflicting report that no significant regional difference was observed in a large, Japanese population-based study.16 To date, the incidence of translocation involving MALT1 in gastric MALT lymphoma has not been studied in Korean populations in spite of the high prevalence of gastric MALT lymphoma compared to Western countries.The clinicopathologic relationship between t(11;18) API2-MALT1 and gastric MALT lymphoma has been analyzed in several previous reports, suggesting that translocation-positive groups are associated with H. pylori eradication failure, local aggressiveness and advanced clinical stage.10,17 In respect to translocationnegative group, occupying majority of gastric MALT lymphoma, instead, other chromosomal aberrations such as numerical aberrations of chromosomes 3, 12, and 18 were observed frequently. 7,18It was revealed that numerical aberrations and API2-MALT1 translocation were detected in mutually exclusive fashion using 5The Korean Journal of Pathology 2009; 43: 5-12 DOI: 10.4132/KoreanJPathol.2009.43.1.5 Background : The incidence and clinical correlation of MALT1 translocation and numerical aberrations in Korean gastric MALT lymphoma patients have been rarely reported. We studied the incidence and clinicopathologic relationship of these chromosomal aberrations in Korean gastric lymphomas. Methods : Seventy-six gastric lymphomas, which consisted of 40 low grade MALT lymphoma, 4 high grade MALT lymphoma and 32 diffuse large B-cell lymphoma (DLBCL) cases, were analyzed for the detection of t(11;18) API2-MALT1, t(14;18) IgH-MALT1 and aneuploidies of chromo...

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Molecular subtyping of gastric MALT lymphomas: implications for prognosis and management

Cited by 69 publications

References 84 publications

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

Differential expression of NF-κB target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism

CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation

Clinicopathologic Study of Chromosomal Aberrations in Gastric Lymphomas of Korean Patients

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