title: Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: a fluorescent in situ hybridization study using a tissue microarray approach.
abstract: Extranodal marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue [MALT] lymphomas) of the gastrointestinal tract have been known to have characteristic chromosomal aberrations including trisomies of chromosomes 3, 12, and 18. However, knowledge of the clinical significance of cytogenetic changes in MALT lymphomas is still limited. In the present study, the frequency of the numeric and structural aberrations of the chromosomes 1, 3, 12, 18 and X and of the MALT1 gene as well as their potential clinical significance were analyzed by using fluorescent in situ hybridization on a tissue microarray containing 257 tissue samples from 203 cases of surgically resected primary gastric lymphomas including 115 cases of MALT lymphomas, 88 cases of diffuse large B-cell lymphomas (DLBCLs, 75 with an associated MALT lymphoma, so-called ex-MALT DLBCL, and 13 de novo), and 54 controls cases of Helicobacter pylori-associated chronic gastritis. Clinical follow-up information was available in 137 cases. Trisomies 1, 3, 12, and 18 were detected in 3.3%, 44.4%, 12.3%, and 19.2% of MALT lymphomas and in 11.1%, 42.2%, 26.5%, and 22.0% of ex-MALT DLBCLs, respectively. In addition, we found gains of the X chromosome in 36.4% of MALT lymphomas, in 34.5% of ex-MALT DLBCLs, and in 36.4% of de novo DLBCLs. Structural and/or numeric abnormalities of the MALT1 gene were observed in 37.0% of MALT lymphomas and in 22.2% of ex-MALT DLBCLs. In de novo DLBCL, trisomies for chromosomes 3, 12, 18, and X were found in 42.9%, 10.0%, 11.1%, and 36.4%, respectively, whereas alterations of MALT1 (namely, translocations) were found in 20.0% of the cases. An unexpected high and previously unreported gain of chromosome X in gastric MALT lymphomas was found. This tumor appears, therefore, to be a genetically unstable neoplasia. Our results point out that t(11;18) and aneuploidy may be both involved in lymphomagenesis and that at least a subset of MALT lymphomas may progress toward high-grade neoplasia.
authors.affiliation: Department of Human Morphology, Section of Human Pathology, University of Insubria, 21100 Varese, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bernasconi
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou-Diamantis
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopolou-Diamantiis
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
authors.forename: Stephan
authors.initials: S
authors.lastname: Dirnhofer
authors.forename: Stephan
authors.initials: S
authors.lastname: Wengmann
authors.forename: Katharyna
authors.initials: K
authors.lastname: Glatz-Krieger
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Luigi
authors.initials: L
authors.lastname: Insabato
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D020169:Caspases / Q000235:genetics; D043171:Chromosomal Instability; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D046888:Tissue Array Analysis; D014178:Translocation, Genetic
chemical_list: D009363:Neoplasm Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein