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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1398-1404
NEOPLASIA
BCL10 mutation does not represent an important
pathogenic mechanism in gastric MALT-type lymphoma, and the presence of
the API2-MLT fusion is associated with aberrant nuclear
BCL10 expression
Brigitte Maes,
Anouk Demunter,
Benjamin Peeters, and
Christiane De
Wolf-Peeters
From the Department of Morphology and Molecular
Pathology, Katholieke Universiteit Leuven, Belgium.
Two recurrent translocations have been associated with
mucosa-associated lymphoid tissue (MALT)-type lymphoma,
t(11;18)(q21;q21) and t(1;14)(p22;q32). The first, t(11;18)(q21;q21),
results in the fusion protein API2-MLT (API2-MALT1). Through
t(1;14)(p22;q32), the BCL10 gene is entirely transferred to
the IgH gene, resulting in its overexpression. Wild-type
BCL10 is implicated in apoptosis, and it has been suggested that
mutated forms gain oncogenic activity. The occurrence of genomic
BCL10 mutations in 35 gastric MALT-type lymphomas with or
without t(11;18)(q21;q21) (10 and 25 cases, respectively) was
investigated. DNA extracted from either whole tissue sections or
microdissected clusters of tumor cells was used. Five polymerase chain
reactions amplifying the coding exons were performed and were
followed by direct sequencing of the products. Twenty differences with
the published BCL10 sequence, all single nucleotide
substitutions, were detected in 16 cases. Of these, 12 represented
known polymorphisms, either at codon 8, 213, or 5. Of the remaining 8 substitutions, 2 were silent and 6 resulted in amino acid
substitutions. Mutation analysis results were correlated with the BCL10
expression pattern. Aberrant nuclear BCL10 expression was detected in
14 cases. No association could be demonstrated between the latter and
the presence of BCL10 mutations. In contrast, all 10 cases
carrying t(11;18)(q21;q21) showed nuclear expression, whereas this
staining pattern was absent in 21 of 25 cases without t(11;18)(q21;q21). These results demonstrate that BCL10
mutations are rare in gastric MALT-type lymphoma and are not related to the aberrant nuclear expression of BCL10. In contrast, they indicate that the presence of the API2-MLT fusion protein is associated with
aberrant nuclear BCL10 expression.
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