Genetic evidence for a clonal link between low and high‐grade components in gastric MALT B‐cell lymphoma

Peng, Huaizheng; Du, M Q; Diss, TC; Isaacson, Peter G.; Pan, Langxing

doi:10.1046/j.1365-2559.1997.5450786.x

Cited by 106 publications

(81 citation statements)

References 28 publications

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“…Some studies are supportive of a lymphomagenesis of high-grade MALT lymphoma from low-grade MALT lymphoma, eg by showing clonal relationship between low-and high-grade lymphoma cells. 3,4,[43][44][45] It might be hypothesised that MALT lymphocytes undergo a sequence of genetic changes that ultimately lead to high-grade MALT lymphoma. In this case, one would expect to find aberrations of the low-grade tumour to be present in the high-grade tumour cells as well.…”

Section: Discussionmentioning

confidence: 99%

True

1999

Leukemia

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Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low-to high-grade cases. Furthermore, its exact relation to primary diffuse large B cell lymphoma (DLBCL) of the stomach is not clear. We applied in situ hybridisation (ISH) with centromeric probes on 43 samples of 39 patients with primary gastric lymphoma (13 samples with low-grade MALT lymphoma, 25 with high-grade MALT lymphoma and five with DLBCL) to detect numerical aberrations of 10 chromosomes. ISH was performed immunohistochemically on nuclei isolated from paraffin-embedded resection tissue and on whole paraffin sections using immunofluorescence. In six of 13 low-grade MALT lymphomas trisomy was detected (46%) and mostly involved chromosome 3 (33%). In high-grade MALT lymphomas, trisomies were found in 16 of 25 cases (64%), mainly involving chromosomes 12 and 18. Trisomy 3 was present in only 13% of these cases. Of five DLBCL, only one showed trisomy. Nine of the 16 aberrant high-grade MALT lymphomas (56%) showed trisomy of more than one chromosome per case vs two of six for low-grade cases. In lymphomas with separate low-and high-grade tumour components some trisomies were detected in both components, whereas others occurred only in the high-grade tumour cells. This supports the hypothesis that high-grade MALT lymphomas can develop from a low-grade type and that this progression is accompanied by the acquisition of more genetic aberrations. However, trisomy 3 probably does not play a major role in this progression.

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Section: Discussionmentioning

confidence: 99%

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1999

Leukemia

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“…They found "unmasked" histologically high-grade disease in all patients [99]. Immunohistochemical studies, as well as PCR of immunoglobulin heavy chain gene rearrangements, demonstrated that the low-and high-grade components derive from the same clone [100].…”

Section: High-grade Gastric Malt Lymphomamentioning

confidence: 99%

Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue

et al. 2006

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“…4 However, the strongest argument for this hypothesis is the demonstration of a clonal relationship between both lymphoma subtypes within the same patient. 5,6 This progression of a low grade MALT lymphoma to a high grade lymphoma has been demonstrated to be associated with the loss of Bcl-2 expression, inactivation of p53 and c-myc rearrangement. [7][8][9][10] It is not likely that all diffuse large B cell lymphomas represent transformed low grade MALT lymphomas, since features of a low grade component are only found in 30% of cases.…”

Section: Introductionmentioning

confidence: 99%

Primary diffuse large B cell lymphoma of the stomach: analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection

et al. 1999

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Gastric low grade MALT lymphomas show a pattern of somatic mutations in their rearranged immunoglobulin genes, indicative of antigen selection. This provides evidence for antigen stimulation in the lymphomagenesis. Gastric diffuse large B cell lymphomas develop secondary to low grade MALT lymphoma or de novo. To study whether antigen-selection is also a feature of primary diffuse large B cell lymphomas, we analysed somatic mutations in the rearranged immunoglobulin heavy chain (IgH) variable genes (VH). The rearranged VH genes of six cases of gastric primary diffuse large B cell lymphoma were amplified from genomic or complementary DNA by a VH gene family-specific polymerase chain reaction method. The PCR products were directly sequenced and were compared to published germline sequences to analyse somatic mutations. Similarly to low grade MALT lymphomas 5/6 primary diffuse large B cell lymphomas show a pattern of somatic mutation in their rearranged VH genes, indicative of antigen selection and suggesting a role for antigens in lymphomagenesis. One case showed bi-allelic VH gene rearrangements, which were nonfunctional due to extensive deletions. Antigen selection could not be demonstrated or excluded. Antigen selection is a common feature in most analysed primary diffuse large B cell lymphomas, although some heterogeneity in the mechanisms involved in the lymphomagenesis of gastric primary diffuse large B cell lymphomas has not been excluded entirely (case 4).

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Genetic evidence for a clonal link between low and high‐grade components in gastric MALT B‐cell lymphoma

Cited by 106 publications

References 28 publications

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Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue

Primary diffuse large B cell lymphoma of the stomach: analysis of somatic mutations in the rearranged immunoglobulin heavy chain variable genes indicates antigen selection

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