Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H pylori in gastric MALT lymphoma.
t(11;18)(q21;q21) is a specific chromosomal translocation associated with mucosa-associated lymphoid tissue (MALT) lymphoma. It fuses the amino terminal of the API2 gene to the carboxyl terminal of the MALT1 gene and generates a chimeric fusion product. Although the translocation is frequently detected in gastric and pulmonary MALT lymphoma, its incidence in MALT lymphomas from other sites is largely unknown. It also remains unknown whether the occurrence of the translocation is influenced by the nature of preceding diseases associated with MALT lymphomas. We screened for t(11; 18)(q21;q21) in 417 cases of MALT lymphoma from 8 major sites by reverse transcription-polymerase chain reaction. t(11;18)(q21;q21) was found at highest frequencies in MALT lymphomas from the lung (38%) and stomach (24%), and at moderate frequencies in those from the conjunctiva (19%) and orbit (14%). However, the translocation was found only rarely in MALT lymphomas from the salivary gland (1%) and was absent in those from the thyroid, skin, liver, and other rare sites, and in immunoproliferative small intestinal disease (IPSID). In gastric MALT lymphoma, t(11;18)(q21;q21) was significantly associated with infection by CagA-positive strains of Helicobacter pylori. As CagA-positive strains of H pylori are much more potent in induction of host inflammatory responses, including activation of neutrophils, which release highly genotoxic oxygen reactive species, we therefore examined neutrophil infiltration in recognized precursors of MALT lymphoma including H pylori-associated gastritis, lymphoepithelial sialadenitis, and Hashimoto thyroiditis. Neutrophil infiltration was prominent in H pylori-associated gastritis but not in lymphoepithelial sialadenitis and Hashimoto thyroiditis. Our results demonstrate that t(11;18)(q21; q21) occurs at markedly variable frequencies in MALT lymphoma of different sites and suggest that the occurrence of the translocation is influenced by the nature of premalignant diseases associated with MALT lymphoma. Oxidative damage might play a role in development of t(11;18)(q21; q21).
Ye
Hongtao
H
Department of Histopathology, University College London, United Kingdom.
Liu
Hongxiang
H
Attygalle
Ayoma
A
Wotherspoon
Andrew C
AC
Nicholson
Andrew G
AG
Charlotte
Frederic
F
Leblond
Veronique
V
Speight
Paul
P
Goodlad
John
J
Lavergne-Slove
Anne
A
Martin-Subero
Jose Ignacio
JI
Siebert
Reiner
R
Dogan
Ahmet
A
Isaacson
Peter G
PG
Du
Ming-Qing
MQ
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial / Q000235:genetics; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001426:Bacterial Proteins / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D004269:DNA, Bacterial / Q000032:analysis; D016480:Helicobacter pylori / Q000254:growth & development / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis; D018375:Neutrophil Activation; D009928:Organ Specificity; D014178:Translocation, Genetic; D014774:Virulence
D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D009363:Neoplasm Proteins; C080866:cagA protein, Helicobacter pylori