Comparative expressed sequence hybridization studies of t(11;18)(q21;q21)-positive and -negative gastric MALT lymphomas reveal both unique and overlapping gene programs

Abstract

Among the genetic abnormalities reported to occur in MALT lymphomas, the translocation t(11;18)(q21;q21) is of particular interest because it is exclusively documented in MALT lymphomas, mainly with gastrointestinal location. It results in the creation of a fusion protein API2-MALT1 that activates the transcription factor NF-jB through enhanced IKKc polyubiquitination. Here, we apply the recently developed molecular technique termed comparative expressed sequence hybridization to identify differentially expressed chromosomal regions related to the pathogenesis of gastric MALT lymphomas. By comparing t(11;18)(q21;q21)-positive gastric MALT lymphomas to their t(11;18)(q21;q21)-negative counterparts, we found that the location of the MALT1 break point determines a difference in expression pattern within the t(11;18)(q21;q21)-positive group. Moreover, we could define a gastric MALT lymphoma signature, which most likely comprises the regions and genes with significance in the development of MALT lymphomas, by comparing both t(11;18)(q21;q21)-positive and -negative MALT lymphomas to normal lymphoid tissue. Finally, a significant imprint of the marginal zone signature, established by comparing microdissected, splenic B follicles with and without marginal zone, was evident in the expression profile of MALT lymphoma, further supporting a marginal zone origin for this type of B-cell non-Hodgkin's lymphoma.

Clinical Trial Report: Eradication of Helicobacter pylori and MALT Lymphoma: Where Do We Stand?

“…The API2 gene inhibits apoptosis whereas the MALT1 gene is believed to have its effect via activation of nuclear factor-κB [4]. This translocation mutation is believed to promote lymphoma cell survival and proliferation [5]. Unfortunately, about 30% of gastric marginal zone B cell lymphomas of MALT type have this mutation which carries a poor prognosis for treatment alone with antibiotics (22.2% remission rate).…”

Extranodal lymphoma: pathogenesis, diagnosis and treatment

“…Interestingly, HP-negative MALT lymphomas have shown a high frequency of positive t(11;18) (q21;q21) [ 72 ]. This translocation event leads to the formation of a fusion protein called API2-MALT1, which in turn activates the transcription factor NF-kappa through enhanced IKK gamma polyubiquitination [ 73 ]. The above findings suggest that t(11;18)(q21;q21) may be a major contributor to the development of gastric MALT lymphoma and is associated with a poor prognosis [ 73 ].…”

New developments in the pathology of malignant lymphoma: a review of the literature published from October 2009 to January 2010

“…The recently described method comparatively expressed sequence hybridization, a sort of comparative genetic hybridization for RNA expression profiles, was used by Sagaert et al [17] to compare t(11,18)-positive and t (11,18)-negative gastric MALT lymphomas, normal gastric mucosa, and microdissected splenic marginal zone cells. They found that the expression profiles differed between the two types of MALT lymphoma and were even different according to the site of the chromosomal breakpoint, but they could also define a MALT-lymphoma signature that differentiates from normal gastric mucosa and a signature that overlaps with splenic marginal zone B cell.…”