Frequent mutation of bcl-6 proto-oncogene in high grade, but not low grade, MALT lymphomas of the gastrointestinal tract.
OBJECTIVE
Knowledge regarding the molecular pathogenesis and histogenesis of gastrointestinal mucosa-associated lymphoid tissue non-Hodgkin's lymphomas (MALT-NHL) is limited. Mutations of BCL-6, a zinc finger transcription factor implicated in lymphoid development, occur frequently in lymphomas and represent a histogenetic marker of B-cell transit through the germinal center. The distribution of BCL-6 mutations in gastrointestinal MALT-NHL was analyzed in this study.


METHODS
This study was based on 26 gastrointestinal MALT-NHL, including 16 cases of low grade histology and 10 cases of high grade histology. Mutations of BCL-6 were investigated by a combination of polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing analysis.


RESULTS
Mutations of BCL-6 occurred in 6/10 high grade MALT-NHL, whereas they were absent from all low grade cases tested (n = 16; p = 0.001). MALT-NHL harboring BCL-6 mutations included 5 cases of gastric MALT-NHL and 1 case of jejunal MALT-NHL. Mutations were predominantly represented by single nucleotide substitutions which were multiple in most cases. All sequence alterations were unique to individual cases of gastrointestinal MALT-NHL.


CONCLUSIONS
Mutations of BCL-6 occur frequently in high grade gastrointestinal MALT-NHL and display characteristics similar to those of BCL-6 mutations harbored by other B-cell lymphomas. The association of high grade MALT-NHL with BCL-6 mutations corroborates their histogenetic derivation from germinal center-related B-cells and may be of potential pathogenetic relevance for these disorders.
Division of Internal Medicine, Department of Medical Sciences, "Amedeo Avogadro" University of Eastern Piedmont, via Solaroli 17, 28100 Novara, Italy. gaidano@med.no.unipmn.it
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G
Gaidano
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Capello
A
A
Gloghini
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L
Fassone
D
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Vivenza
C
C
Ariatti
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Migliazza
G
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Saglio
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Carbone
D004268:DNA-Binding Proteins / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005787:Gene Frequency; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors