Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1032-1038
Detection of aberrant isotype switch recombination in
low-grade and high-grade gastric MALT lymphomas
Elena Nardini,
Antonella Aiello,
Roberto Giardini,
Maria Ines Colnaghi,
Sylvie Ménard, and
Andrea Balsari
From the Molecular Targeting Unit, Department of Experimental
Oncology, Department of Pathology and Cytology, National Cancer
Institute, Milan, Italy, and Institute of Pathology, University of
Milan, Milan, Italy.
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma originates
from reactive lymphocytic infiltrates during chronic gastritis, closely
associated with Helicobacter pylori infection. MALT lymphomas
may be either "low grade" or "high grade," and transformation from low grade to high grade can occur. To obtain information on the maturational state of MALT lymphoma cells, we
investigated their ability to undergo isotype switch recombination, which together with immunoglobulin variable gene somatic mutation, contributes to normal B-cell maturation. Using specific probes for the
immunoglobulin heavy-chain (IgH) switch regions, we found by Southern
blot that 3 out of 5 low-grade cases and 2 out of 2 high-grade cases
showed rearrangements within IgH switch regions, which appeared
aberrant in 4 of the 5 cases. The cloning of two rearranged
fragments from one low-grade and one high-grade case confirmed
the aberrant nature of the rearranged fragments. A deletion from
the switch µ region (Sµ) to the first constant µ exon
(Cµ 1) and a second deletion from the second constant µ exon
(Cµ 2) to the gamma 3 region (
3) was detected in the low-grade
case. In the high-grade case, there was a deletion of the IgH intronic enhancer (Eµ) and a 336-base pair (bp) insertion into the Sµ
region of a gene (KIAA0307) normally located at 15q24. These data
demonstrate for the first time the ability of MALT lymphoma cells to
undergo aberrant isotype switch recombinations, which might be directly involved in the development or progression of malignancy.
