Detection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas.
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 mu region (S mu) to the first constant mu exon (C mu 1) and a second deletion from the second constant mu exon (C mu 2) to the gamma 3 region (gamma 3) was detected in the low-grade case. In the high-grade case, there was a deletion of the IgH intronic enhancer (E mu) and a 336-base pair (bp) insertion into the S mu 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.
Nardini
E
E
Molecular Targeting Unit, Department of Experimental Oncology, National Cancer Institute, Milan, Italy.
Aiello
A
A
Giardini
R
R
Colnaghi
M I
MI
Ménard
S
S
Balsari
A
A
D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005091:Exons / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007438:Introns / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D045567:VDJ Recombinases
D004273:DNA, Neoplasm; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases