Methylation of &lt;i&gt;p&lt;/i&gt;16&lt;sup&gt;INK4A&lt;/sup&gt; and Mitotic Arrest Defective Protein 2 (&lt;i&gt;MAD&lt;/i&gt;2) Genes in Gastric Marginal-Zone B-Cell Lymphomas

Park, Sanghui; Kim, Kyoung Mee; Kim, Jae J.; Lee, Jun Haeng; Rhee, Jong Chul; Ko, Young Hyeh

doi:10.1159/000195698

Cited by 12 publications

(10 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that P16 is underexpressed more frequently in gastric MALT than in other lymphoma types [20,21]. This has been shown to primarily relate to p16 promoter hypermethylation in non-transformed MALTs [20,36,37].…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal lymphomas in a North American population: clinicopathologic features from one major Central-Midwestern United States tertiary care medical center

et al. 2012

View full text Add to dashboard Cite

BackgroundGastrointestinal (GI) lymphomas are very common types of extranodal lymphomas, and we hypothesize there are regional differences in subtype, distribution in the GI tract, and epidemiological features among the different populations.MethodsWe retrospectively evaluated the clinical, molecular and histologic features of North American primary and secondary GI lymphomas diagnosed from 2000–2009 seen at our institution. We utilized immunohistochemistry and fluorescence in situ hybridization to further evaluate a subset of the gastric lymphomas.ResultsExtranodal marginal zone lymphomas of mucosal associated lymphoid tissue (MALTs) and diffuse large B cell lymphomas (DLBCLs) were the most common subtypes of GI lymphomas. Select gastric DLBCLs (N = 6) and MALTs (N = 13) were further examined for API2-MALT1 and IGH translocations, and P16 and P53 protein expression. Gastric MALTs showed frequent API2-MALT1 (38%) but not IGH translocations (0%), and the DLBCLs showed neither translocation. Expression of P16 and P53 proteins and the proliferative index were compared between high grade gastric lymphomas (gastric DLBCLs) and low grade gastric lymphomas (gastric MALTs). P53 overexpression (P = 0.008) and a high proliferation index [Ki-67] (P = 0.00042) were significantly associated with gastric DLBCL, but no statistically significant difference was observed in P16 expression (p = 0.108) between gastric DLBCL and gastric MALT.ConclusionOur study revealed that GI lymphomas from a Central-Midwestern North American population showed differences and similarities to non-North American cohorts. In addition, API2-MALT1, P16 and P53 abnormalities occurred frequently in gastric lymphomas from this North American population.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1415505838687793

show abstract

Section: Discussionmentioning

confidence: 99%

Gastrointestinal lymphomas in a North American population: clinicopathologic features from one major Central-Midwestern United States tertiary care medical center

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The silenced tumor suppressor genes further drive these cells to undergo malignant transformations through the abnormal promotion of cell proliferation and cell cycle alterations [68,69,70]. For gastric lymphoma, several studies have reported that the methylation of p16 INK4A , an inhibitor of cyclin-dependent kinases, may be associated with the development of gastric MALT lymphomas [71,72,73]. Kim et al reported that p16 hypermethylation was detected in seven (58%) of 12 patients with HP-dependent gastric MALT lymphoma [71].…”

Section: Epigenetic Changes and Genetic Changes Are Involved In Thmentioning

confidence: 99%

Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Kuo

Yeh

et al. 2019

Cancers

View full text Add to dashboard Cite

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B-cells. Furthermore, the reason why the antigen stimuli of these intratumoral T-cells with tonic B-cell receptor signaling promote lymphomagenesis of gastric MALT lymphoma has also been investigated. In addition to the aforementioned mechanisms, it has been demonstrated that the translocated HP cytotoxin-associated gene A (CagA) can promote B-cell proliferation through the activation of Src homology-2 domain-containing phosphatase (SHP-2) phosphorylation-dependent signaling, extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), B-cell lymphoma (Bcl)-2, and Bcl-xL. Furthermore, the expression of CagA and these CagA-signaling molecules is closely associated with the HP-dependence of gastric MALT lymphomas (completely respond to first-line HPE). In this article, we summarize evidence of the classical theory of HP-reactive T-cells and the new paradigm of direct interaction between HP and B-cells that contributes to the HP-dependent lymphomagenesis of gastric MALT lymphomas. Although the role of first-line HPE in the treatment of HP-negative gastric MALT lymphoma remains uncertain, several case series suggest that a proportion of HP-negative gastric MALT lymphomas remains antibiotic-responsive and is cured by HPE. Considering the complicated interaction between microbiomes and the genome/epigenome, further studies on the precise mechanisms of HP- and other bacteria-directed lymphomagenesis in antibiotic-responsive gastric MALT lymphomas are warranted.

show abstract

“…[56][57][58] Park et al demonstrated that p16 INK4A methylation occurred more frequently in t(11;18)(q21;q21)-negative gastric MALT lymphoma, whereas methylation of the MAD2 gene was associated with BCL10 expression. 58 In a recent study on the relationship between the CpG-island-methylator phenotype (CIMP) and gastric lymphoma, Kondo et al showed that H pylori-positive gastric lymphoma was associated with a significantly higher incidence of CIMP (93%, 27/29) than that of H pylori-negative gastric lymphoma (42%, 5/12; P Ͻ .001). 59 Aberrant CpG methylation of certain genes, such as p16, MGMT, and MINT31, was associated with H pylori infection.…”

Section: Direct Effects Of H Pylori On B-cell Proliferation In Gastrimentioning

confidence: 99%

Helicobacter pylori and mucosa-associated lymphoid tissue: what's new

Kuo

Cheng

2013

Hematology

View full text Add to dashboard Cite

Methylation of <i>p</i>16<sup>INK4A</sup> and Mitotic Arrest Defective Protein 2 (<i>MAD</i>2) Genes in Gastric Marginal-Zone B-Cell Lymphomas

Cited by 12 publications

References 62 publications

Gastrointestinal lymphomas in a North American population: clinicopathologic features from one major Central-Midwestern United States tertiary care medical center

Gastrointestinal lymphomas in a North American population: clinicopathologic features from one major Central-Midwestern United States tertiary care medical center

Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Helicobacter pylori and mucosa-associated lymphoid tissue: what's new

Contact Info

Product

Resources

About