Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue

doi:10.1016/0165-4608(92)90130-Z

Cancer Genetics and Cytogenetics

Volume 58, Issue 1, January 1992, Pages 35-38

https://doi.org/10.1016/0165-4608(92)90130-Z Get rights and content

Abstract

The recently described B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) form a distinct clinico-pathologic group of non-Hodgkin's lymphoma, and therefore would be expected to be characterized by a recurrent chromosomal aberration. We have analyzed the cytogenetics of 23 cases of MALT lymphomas arising in the stomach, small intestine, lung, and lacrimal gland. In each case the presence of an abnormal clonal cell population was confirmed by the identification of rearranged bands when digested tumor DNA was hybridized with a probe to the joining region of the immunoglobulin heavy chain gene. Metaphase spreads were obtained in 14 cases, of which 9 cases showed an abnormal karyotype. Although no unifying aberration was detected, rearrangements of chromosome 1p, and numerical abnormalities of chromosomes 3 and 7, may play a role in the genesis of these tumors.

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Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment
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Over the last decades, we have witnessed an increase in the incidence of primary ocular adnexa lymphomas (POALs) probably because advances in imaging techniques have enabled precise biopsies of the tumors. The ocular tissue biopsy, before the initiation of the appropriate treatment, is mandatory and necessary for a correct diagnosis of POALs by the use of immunophenotyping and a correct molecular classification. Only in a minority of cases the ocular adnexa are secondarily affected by a systemic disease. Among the POALs, the most common is the primary extra nodal lymphoma of MALT-type (POAML). POAML is rarely symptomatic in the early phase of the disease. As a consequence, often we see a delay in ophthalmic consultations and diagnosis. The clinical manifestations are heterogeneous and its management requires a multidisciplinary approach involving ophthalmologists, hematologists and radiotherapists.
Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities
2012, Modern Pathology
Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas. Overall, 90% exhibited copy-number abnormalities. Lymphoplasmacytic lymphomas demonstrated the most complex karyotype (median=7 copy-number abnormalities), followed by MALT (4), nodal (3.5) and splenic marginal zone lymphomas (3). A comparative analysis exposed a group of copy-number abnormalities shared by several or all the entities with few disease-specific abnormalities. Gain of chromosomes 3, 12 and 18 and loss of 6q23-q24 (TNFAIP3) were identified in all entities. Losses of 13q14.3 (MIRN15A-MIRN16-1) and 17p13.3-p12 (TP53) were found in lymphoplasmacytic and splenic marginal zone lymphomas; loss of 11q21-q22 (ATM) was found in nodal, splenic marginal zone and lymphoplasmacytic lymphomas and loss of 7q32.1-q33 was found in MALT, splenic and lymphoplasmacytic lymphomas. Abnormalities affecting the nuclear factor kappa B pathway were observed in 70% of MALT and lymphoplasmacytic lymphomas and 30% of splenic and nodal marginal zone lymphomas, suggesting distinct roles of this pathway in the pathogenesis/progression of these subtypes. Elucidation of the genetic alterations contributing to the pathogenesis of these lymphomas may guide to design-specific therapeutic approaches.
Functional copy number changes in Sézary syndrome: toward an integrated molecular cytogenetic map III
2008, Cancer Genetics and Cytogenetics
Citation Excerpt :
Intriguingly, in this study, the gene cluster of copy number losses at 1p36.33p22.1, which separate SS from NC, also contains LCK, suggesting it may have a potentially functional role in the pathogenesis of SS. The BCL10 gene, which was identified by its translocation in mucosa-associated lymphoid tissue lymphoma [45,46], encodes a predicted protein of 233 amino acids and is a cellular homolog of the equine herpesvirus-2 gene (E10), both of which contain an amino-terminal caspase recruitment domain homologous to that found in several apoptotic molecules, and BCL10 was found to be expressed as a 4.2-kilobase transcript in all normal and malignant tissues examined (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id = 603517). In addition, a previous immunohistochemistry study has demonstrated aberrant BCL10 protein expression in nasal NK/T-cell lymphoma [47].
Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphomas (CTCL) manifested by generalized exfoliative erythroderma, intense pruritus, peripheral lymphadenopathy, and abnormal hyperchromatic mononuclear cells in the skin, lymph nodes, and peripheral blood. Previous studies have revealed complex genetic aberrations affecting almost all chromosomes with up- and down-regulation of several genes in this subtype of CTCL. It is still unclear, however, which of these genetic alterations are the primary changes and which are the secondary ones. We have long thought that a key molecular defect should be consistently present at DNA, RNA, and protein levels. We therefore assume that some chromosome copy number changes (CNC) seen in cancer cells may have a direct impact on gene expression pattern and that these CNC are presumably functional. To test this hypothesis, we designed a simple but novel boinformatic method that included analysis of SS gene expression microarray raw data, generation of gene lists from the chromosomal regions showing significant CNC in SS, and data remining to establish if the CNC gene lists affected gene clustering in terms of separation of SS cases from the normal controls or not. The bioinformatic analysis of 17 selected gene lists with GeneSpring software showed that four (24%) from copy number losses at 1p36p22, 6q24, and 15q11.2, as well as gains at 22q11.2q13.3, were capable of separating all six SS cases from two controls (P < 0.05), and some of the genes, such as LCK at 1p34.3, may have implications in CTCL. The remaining 13 gene lists produced a mixed gene clustering patterns between SS cases and normal control samples (P ≪ 0.01). These findings suggest that CNC from these chromosomal regions may be functional and relevant to SS.
Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: a fluorescent in situ hybridization study using a tissue microarray approach
2008, Human Pathology
Extranodal marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue [MALT] lymphomas) of the gastrointestinal tract have been known to have characteristic chromosomal aberrations including trisomies of chromosomes 3, 12, and 18. However, knowledge of the clinical significance of cytogenetic changes in MALT lymphomas is still limited. In the present study, the frequency of the numeric and structural aberrations of the chromosomes 1, 3, 12, 18 and X and of the MALT1 gene as well as their potential clinical significance were analyzed by using fluorescent in situ hybridization on a tissue microarray containing 257 tissue samples from 203 cases of surgically resected primary gastric lymphomas including 115 cases of MALT lymphomas, 88 cases of diffuse large B-cell lymphomas (DLBCLs, 75 with an associated MALT lymphoma, so-called ex-MALT DLBCL, and 13 de novo), and 54 controls cases of Helicobacter pylori–associated chronic gastritis. Clinical follow-up information was available in 137 cases. Trisomies 1, 3, 12, and 18 were detected in 3.3%, 44.4%, 12.3%, and 19.2% of MALT lymphomas and in 11.1%, 42.2%, 26.5%, and 22.0% of ex-MALT DLBCLs, respectively. In addition, we found gains of the X chromosome in 36.4% of MALT lymphomas, in 34.5% of ex-MALT DLBCLs, and in 36.4% of de novo DLBCLs. Structural and/or numeric abnormalities of the MALT1 gene were observed in 37.0% of MALT lymphomas and in 22.2% of ex-MALT DLBCLs. In de novo DLBCL, trisomies for chromosomes 3, 12, 18, and X were found in 42.9%, 10.0%, 11.1%, and 36.4%, respectively, whereas alterations of MALT1 (namely, translocations) were found in 20.0% of the cases. An unexpected high and previously unreported gain of chromosome X in gastric MALT lymphomas was found. This tumor appears, therefore, to be a genetically unstable neoplasia. Our results point out that t(11;18) and aneuploidy may be both involved in lymphomagenesis and that at least a subset of MALT lymphomas may progress toward high-grade neoplasia.
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^☆: This project was supported by the Sir Jules Thorn Charitable Trust and The Cancer Research Campaign.

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Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue☆

Abstract

Extranodal lymphomas

Primary B cell gastric lymphoma

Hum Pathol

Primary B cell gastric lymphoma—a reassessment of its histogenesis

J Pathol

Immunoproliferative small-intestinal disease, an immunohistochemical study

Am J Pathol

Primary pulmonary lymphoma: a reappraisal of its histogenesis and its relationship to pseudolymphoma and interstitial pneumonia

Histopathology

Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis

Hum Pathol

Primary B cell lymphoma of salivary glands and its relationship to myoepithelial sialadenitis (MESA)

Human Pathol

Low grade B cell lymphoma of mucosa associated lymphoid tissue arising in the thymus—a thymic lymphoma mimicking myoepithelial sialadenitis

Am J Surg Pathol

The bcl-2 gene in primary B cell lymphoma of mucosa associated lymphoid tissue (MALT)

Am J Pathol

Follicular colonization in B cell lymphoma of mucosa associated lymphoid tissue

Am J Surg Pathol

A genotypic study of low grade B-cell lymphomas, including lymphomas of mucosa associated lymphoid tissue (MALT)

J Pathol

Molecular analysis of the t(14;18) chromosome translocation in malignant lymphomas

N Eng J Med

The sequence of an immunoglobulin epsilon heavy chain constant region gene and evidence of three non-allelic genes

EMBO J