Recent Advances in the Genetic of MALT Lymphomas

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.

Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma

“…The t(11;18)(q21;q21) translocation, a trigger for NF-κB activation, was more frequently observed in cases of HP-negative MALT lymphoma than in those of HP-positive MALT lymphoma, and NF-κB signaling contributes to the antibiotic unresponsiveness of gastric MALT lymphoma [ 13 , 42 , 43 , 118 , 119 ]. Our previous study also demonstrated that nuclear expression of NF-κB was significantly associated with the antibiotic-unresponsiveness of gastric MALT lymphoma [ 45 , 120 , 121 ].…”

Genetics Abnormalities with Clinical Impact in Primary Cutaneous Lymphomas

“…When the marginal zone lymphoid infiltrate becomes genetically unstable, that is, it acquires genetic alterations such as trisomy 3, trisomy 18, t(1;14)(p22;q32), t(11;18)(q21;q21), t(14;18)(q32;q21)-IgH/MALT, t(3;14)(q27;q32), t(3;14)(p14.1;q32) or FAS mutations, the lymphomatous transformation occurs. Such cytogenetic alterations observed in all MALT lymphomas are detected in a limited number of pBCLm cases (see Table 6 ) [ 70 , 71 ].…”

Primary hepatopancreatobiliary lymphoma: Pathogenesis, diagnosis, and management

“…Meanwhile, activated MALT1 has protease activities, causing hydrolyzation of tumor necrosis factor alpha inducible protein 3 (TNFAIP3), which act as a NF-κB negative regulator, further promoting NF-κB activation. Overexpression of MALT1 and BCL-10 can upregulate the BAFF expression, thus enhancing the activation of the non-canonical NF-κB pathway ( Figure 1 ) ( 27 ).…”

“…TNFAIP3 plays a key role in the regulation of several inflammation signaling pathways, which can negatively regulate the NF-κB pathway by inhibiting signals from various surface receptors to activate the signaling pathway. Therefore, the inactivating mutation or deletion of TNFAIP3 gene can downregulate its expression and reduce the repression of NF-kB activation ( Figure 1 ) ( 18 , 27 ). Such genetic abnormalities play an essential role in lymphomagenesis.…”

“…API2/MALT1 fusion can reduce the inhibition of API2 on apoptosis response to antigen stimulation, thus leading to MALT lymphoma of the biliary tract ( 108 ). Its production can also induce expression of BCL-10 and activation of the NF-κB pathway, leading to cell proliferation ( Figure 1 ) ( 27 ). Another possible mechanism is that prolonged chronic inflammation causes irreversible genetic rearrangements, thus disabling the response of cells to IL-2 regulation, eventually helping in the development of MALT lymphoma ( 114 ).…”