Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma.
Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occur in a number of anatomic sites, but share overlapping morphologic and immunophenotypic features. Helicobacter pylori infection has been identified as an etiologic factor in gastric MALT lymphoma, and a growing list of other infectious organisms have recently been shown to be associated with MALT lymphomas at other anatomic sites. Although cause and effect has not been established for most of these infectious agents, our understanding of the biology has significantly improved, in part through the application of standard cytogenetic analyses. The common karyotypic alterations that characterize MALT lymphomas include the trisomies 3 and 18, the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(q27;q32), and the recently described t(3;14)(p14.1;q32). This apparent complexity of cytogenetic alterations that have now been implicated in the pathogenesis of extranodal MALT lymphoma serves as a paradigm for molecular cross talk in neoplastic disease. Recent data have shown that at least three of the disparate translocations affect a common signaling mechanism, and thus unify all three under a common pathogenesis, resulting in the constitutive activation of the nuclear factor kappa B (NF-kappaB) pathway. It may be that the new MALT-related translocation involving the FOXP1 gene and other as yet undiscovered translocations may all have in common increased NF-kappaB signaling.
Farinha
Pedro
P
Department of Pathology, British Columbia Cancer Agency, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada.
Gascoyne
Randy D
RD
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008967:Molecular Biology; D009154:Mutation; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human