Microsatellite instability in gastric MALT lymphoma

Abstract

The role of microsatellite instability and defects in DNA mismatch repair mechanism in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is still controversial, as both negative and positive findings have been reported. This may be explained mainly by arbitrary selection of the tested loci, the use of various techniques of microsatellite instability analysis and by different definitions of replication error positive phenotype. The aim of our study was to evaluate the instability at selected microsatellite markers using the GeneScan Analysis Software. DNA from paraffin-embedded tissue blocks of 13 previously untreated patients with localized gastric MALT lymphoma was extracted. Five microsatellite markers, which are located in hMSH2, hMLH1, P16, APC and MLL loci, were selected from the genetic database. We found genetic instability in tumors of 9/13 patients with gastric MALT lymphoma (69%). Seven of them had replication-error-positive phenotype (54%). Microsatellite instability was found in 39% of the samples in the MLL locus, 39% in the APC, 46% in the P16, 23% in the hMLH1 and none in the hMSH2. This study demonstrates that microsatellite instability has more prominent role in pathogenesis of gastric MALT lymphoma than reported to date. We suggest that microsatellite instability should be analyzed with markers adjacent to chromosomal loci that are involved in lymphomas. Our findings support the 'Real Common Target genes' theory of high rate of microsatellite instability in specific genes, which are associated with related tumors.

Helicobacter pylori and Gastric Malignancy

“…Obviously, microsatellite instability and defects in DNA mismatch repair mechanism are also involved in the pathogenesis of gastric MALT lymphoma. Nine of 13 patients with gastric MALT lymphoma (69%) revealed microsatellite instability [18]. Seven of them had replication‐error‐positive phenotype.…”

Microsatellite Instability and Promoter Hypermethylation of DNA repair genes in Hematologic Malignancies: a forthcoming direction toward diagnostics

“…For the first time, this study established a MSI-positive Burkitt's lymphoma cell line NAMALWA, capable of correcting base-base alterations and/or insertion-deletion loops with high efficacy despite faulty DNA MMR system [19]. Studies on patient samples showed an increased frequency of loss of expression in MSH2 and MLH1 genes by immunohistochemical staining, indicating the presence of MSI in chronic B cell lymphocytic leukemia [20]. All of the above experiments show the dynamism of cancers and compel us to consider MSI as a part of hematologic malignancies.…”

The Role of Anti-Helicobacter Pylori Therapy in Remission Induction of Primary Gastric Lymphoma by Analysis of Microsatellite Instability

“…Certain genetic aberration were found to be associated with gastric MALT lymphoma including trisomy 3, trisomy 5, trisomy 18, t [11,18] (q21,q21) as well as mutation in p53 and p16 which are linked to DLBCL [3,17,18].…”

“…Microsatellites are short repeat sequences dispersed throughout the genome. Defects in the DNA repair are reflected by DNA microsatellite instability [18]. Microsatellite instability is used to identify genetic loci that have been lost to detect genomic alterations and to evaluate the contribution of the mutator pathway to the gastric lymphoma pathogenesis [3,18].…”