Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways

• Published in: Blood Vol. 99; no. 1; pp. 3 - 9
• Main Authors: Starostik, Petr, Patzner, Jochen, Greiner, Axel, Schwarz, Stephan, Kalla, Jörg, Ott, German, Müller-Hermelink, Hans Konrad
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-01-2002; The Americain Society of Hematology
• Subjects: Adult; Aged; Biological and medical sciences; Chromosome Aberrations; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 3; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Amplification; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Loss of Heterozygosity; Lymphoma, B-Cell, Marginal Zone - genetics; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Medical sciences; Microsatellite Repeats; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Translocation, Genetic; Tumors; Chromosomal aberration; Human; Stomach; Prognosis; Pathogenesis; Marginal zone lymphoma; Malignant hemopathy; B-Lymphocyte; Large cell lymphoma; Malignant tumor; Non Hodgkin lymphoma; Abnormal chromosome E18; MALT lymphoma; Lymphoproliferative syndrome; Low malignancy; Cytogenetics; Digestive diseases; Abnormal chromosome; Genetics; Evolution; Abnormal chromosome C11; Gastric disease; High malignancy; Chromosome translocation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.1.3

Low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type can transform into high-grade diffuse large B-cell lymphoma (DLBCL). Up to 60% of the MALT lymphomas contain the recently described t(11;18). However, this translocation has not been detected in any DLBCL so far. To elucidate the pathogenesis of these tumors, microsatellite screening of 24 gastric MALT lymphomas was performed and the results were compared with aberrations detected in a previous study on gastric DLBCL. The most frequent aberration, found in 21% of the MALT lymphomas that were exclusively t(11;18)-negative cases, was amplification of the 3q26.2-27 region (harboring the locus of the BCL6 gene). Allelic imbalances in regions 3q26.2-27, 6q23.3-25, 7q31, 11q23-24, and 18q21 were shared by both MALT lymphoma and DLBCL. Loss of heterozygosity in regions 5q21 (APC gene locus), 9p21 (INK4A/ARF), 13q14 (RB), and 17p13(p53) and allelic imbalances in 2p16, 6p23, and 12p12-13 occurred exclusively in DLBCL. Only one of 10 t(11;18)-positive MALT lymphomas showed an additional clonal abnormality. These tumors thus display features of a clonal proliferation characterized by the presence of the t(11;18). However, they only rarely display secondary aberrations and do not seem to transform into DLBCL. In contrast, t(11;18)-negative MALT lymphomas show numerous allelic imbalances—some of them identical with aberrations seen in DLBCL—suggesting that this group is the source of tumors eventually transforming into high-grade DLBCL.