T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphorna that expresses nuclear BCL10

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphom a is a multistep process and can be clinico-pathologically divided into Hel icobacter pylori-associated gastritis, low-grade tumors, and high-grade tum ors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(1 1;18)(q21; q21) and t(1;14)(p22;q32) has provided fresh insights into the p athogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transc ript 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), sugges ting an important role for BCL10 in lymphoma development. Thirty-three case s 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 trans cription-polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2-MALT1 fus ion 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 ca ses, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed di ssemination 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% a nd 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 a nd that their oncogenic activities may be related to each other.