T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10.
The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multistep process and can be clinico-pathologically divided into Helicobacter pylori-associated gastritis, low-grade tumors, and high-grade tumors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(11;18)(q21;q21) and t(1;14)(p22;q32) has provided fresh insights into the pathogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transcript between the API2 and the MALT1 genes, whereas t(1;14) (p22;q32) causes aberrant nuclear BCL10 expression. Significantly, nuclear BCL10 expression also occurs frequently in MALT lymphomas without t(1;14)(p22;q32), suggesting an important role for BCL10 in lymphoma development. Thirty-three cases of H pylori gastritis, 72 MALT lymphomas, and 11 mucosal diffuse large B-cell lymphomas (DLBCL) were screened for t(11;18)(q21;q21) by reverse transcription-polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2--MALT1 fusion transcript was not detected in H pylori gastritis and mucosal DLBCL but was found in 25 of 72 (35%) MALT lymphomas of various sites. Nuclear BCL10 expression was seen in 28 of 53 (53%) of MALT lymphomas. Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%). Furthermore, t(11;18)(q21;q21) closely correlated with BCL10 nuclear expression. These results indicate that both t(11;18)(q21;q21) and BCL10 nuclear expression are associated with advanced MALT lymphoma and that their oncogenic activities may be related to each other. (Blood. 2001;98:1182-1187)
Liu
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Department of Histopathology, Royal Free and University College Medical School, London, United Kingdom.
Ye
H
H
Dogan
A
A
Ranaldi
R
R
Hamoudi
R A
RA
Bearzi
I
I
Isaacson
P G
PG
Du
M Q
MQ
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015415:Biomarkers / Q000032:analysis; D002869:Chromosome Aberrations / Q000473:pathology; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*
C415943:API2-MALT1 fusion protein, human; D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D015415:Biomarkers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger