title: Characteristic pattern of chromosomal gains and losses in marginal zone B cell lymphoma detected by comparative genomic hybridization.
abstract: Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non-Hodgkin's lymphoma, which has been recently recognized and defined as a disease entity. We investigated 25 cases (18 at primary diagnosis and seven during the course of disease) of MZBCL by comparative genomic hybridization (CGH) and compared these results with cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data. Twenty of the 25 cases (80%) showed gains (total 49) or losses (total 15) of genetic material. In extranodal, nodal, and splenic MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (16%) was most frequently gained, whereas losses predominantly involved chromosomes 17 (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and 18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and 8q and losses of chromosome 17 or 17p occurred more frequently in relapsed or progressive lymphomas. For all of the frequently affected chromosomes, CGH allowed narrowing of the relevant subregions including 3q21-23, 3q25-29 and 18q21-23. By Southern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were found to be a part of the over-represented regions in two cases, one case, and two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH revealed chromosomal imbalances which were not detected by cytogenetic analysis but could be confirmed by FISH or Southern blot analysis in all cases investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and deletion 7q in three cases with a low proportion of tumor cells bearing these abnormalities, as shown by interphase FISH. The characteristic pattern of chromosomal gains and losses detected in this study confirms the distinct nature of MZBCL and may point to chromosomal regions involved in the pathogenesis of these neoplasms.
authors.affiliation: Center for Human Genetics and Flanders Institute of Biotechnology, University of Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Dierlamm
authors.forename: C
authors.initials: C
authors.lastname: Rosenberg
authors.forename: M
authors.initials: M
authors.lastname: Stul
authors.forename: S
authors.initials: S
authors.lastname: Pittaluga
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: L
authors.initials: L
authors.lastname: Michaux
authors.forename: M
authors.initials: M
authors.lastname: Dehaen
authors.forename: G
authors.initials: G
authors.lastname: Verhoef
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: W
authors.initials: W
authors.lastname: de Kelver
authors.forename: T
authors.initials: T
authors.lastname: Bakker-Schut
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: A K
authors.initials: AK
authors.lastname: Raap
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: H
authors.initials: H
authors.lastname: Van den Berghe
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019254:Genes, bcl-2; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics; D014314:Trisomy
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors