title: Frequent allelic imbalance but infrequent microsatellite instability in gastric lymphoma.
abstract: Specific defects in DNA repair pathways are reflected by DNA microsatellite instability (MSI) and play an important role in carcinogenesis. Reported frequencies in gastric non-Hodgkin's lymphomas (NHL) vary from 14% to as high as 90%. Another form of genetic instability in tumours is allelic imbalance (AI) due to loss or gain of genetic material at a specific chromosomal region. This might point to the presence of a tumour suppressor gene or oncogene. We examined both MSI and AI in 26 gastric lymphomas (10 low-grade and 13 high-grade MALT lymphomas and three cases lacking MALT features and categorised as diffuse large B cell lymphoma (DLCL)). Tumour components and normal cells (epithelium, muscle) were microdissected from paraffin-embedded resection samples. Contrary to other studies we did not observe frequent MSI when investigating 18 different loci distributed over 12 chromosomes. Microsatellite instability of a single locus was found in 1/10 (10%) low-grade MALT lymphomas and 2/13 (15%) high-grade MALT lymphomas. These data indicate that DNA mismatch repair genes do not play a role in the pathogenesis of these lymphomas. Allelic imbalance was detected in 60% (6/10) of low-grade MALT lymphomas, in 62% (8/13) of high-grade MALT lymphoma and in 67% (2/3) of DLCL. In high-grade lymphomas more loci showed AI (one to seven loci, with a mean of 2.5 loci per case) than in the low-grade lymphomas (one to two loci, with a mean of 1.3 loci per case), possibly reflecting an increased genomic instability.
authors.affiliation: Department of Pathology, Leiden University Medical Center, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Hoeve
authors.forename: S C
authors.initials: SC
authors.lastname: Ferreira Mota
authors.forename: E
authors.initials: E
authors.lastname: Schuuring
authors.forename: W J
authors.initials: WJ
authors.lastname: de Leeuw
authors.forename: A
authors.initials: A
authors.lastname: Chott
authors.forename: J P
authors.initials: JP
authors.lastname: Meijerink
authors.forename: P M
authors.initials: PM
authors.lastname: Kluin
authors.forename: J H
authors.initials: JH
authors.lastname: van Krieken
mesh_terms: D004252:DNA Mutational Analysis; D004848:Epithelium / Q000378:metabolism; D016259:Genes, myc / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000145:classification / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D009132:Muscles / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013274:Stomach Neoplasms / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D051028:bcl-2-Associated X Protein
chemical_list: D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein