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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1182-1187
NEOPLASIA
T(11;18)(q21;q21) is associated with advanced mucosa-associated
lymphoid tissue lymphoma that expresses nuclear BCL10
Hongxiang Liu,
Hongtao Ye,
Ahmet Dogan,
Renzo Ranaldi,
Rifat A. Hamoudi,
Italo Bearzi,
Peter G. Isaacson, and
Ming-Qing Du
From the Department of Histopathology, Royal Free and
University College Medical School, London; the Cancer Gene Cloning
Center, Institute of Cancer Research, Sutton, United Kingdom; and the
Department of Pathology, Institute of Pathological Anatomy and
Histopathology, Ancona, Italy.
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.
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