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1.
Cancer Genet Cytogenet ; 156(2): 122-8, 2005 Jan 15.
Article in English | MEDLINE | ID: mdl-15642391

ABSTRACT

The cytogenetics of splenic marginal zone lymphoma (SMZL) is less well characterized than the cytogenetics of other non-Hodgkin B-cell lymphomas. The aim of this study was to address this issue by identifying characteristic copy number imbalances in SMZL, for which purpose we analyzed 20 SMZL cases by comparative genomic hybridization (CGH), adding chromosome banding and fluorescence in situ hybridization (FISH) in some cases. CGH identified copy number imbalances in 70% of the cases. Imbalances were recurrently observed for chromosomes 3 (20%), 6 (20%), 7 (25%), 12 (20%), and 14 (10%). The minimally involved regions of these chromosomes were gains of 3q25 approximately qter and 12q13 approximately q15, and loss of 6q23, 7q31, and 14q22 approximately q24. A compilation of our data with data from 3 previous SMZL CGH studies revealed a significant heterogeneity between the studies. Eleven imbalances were recurrently observed in the compiled data set, as opposed to only 5 in our data set. The most frequently observed imbalances in the 73 SMZL cases of the compiled data set were gains of 3q (27%) and 12q (15%), and loss of 7q (18%). Our data suggest that SMZL constitute a genetically heterogeneous disease where gain of 3q25 and loss of 7q31 are the most likely imbalances to be involved in the pathogenesis of the disease.


Subject(s)
Chromosome Aberrations , Lymphoma, B-Cell/genetics , Splenic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Chromosome Mapping , DNA, Neoplasm/genetics , DNA, Neoplasm/isolation & purification , Humans , In Situ Hybridization, Fluorescence , Lymphoma, B-Cell/pathology , Male , Middle Aged , Nucleic Acid Hybridization/methods
2.
Eur J Haematol ; 72(6): 390-402, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15128417

ABSTRACT

To further characterise the genetic background of the two closely related B-lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase-fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13-31 (19%) and loss of 7q22-q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unusual for low-malignant B-cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)-markers SHGC-3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase-FISH investigation we showed the minimal lost 7q-region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase-FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 7 , Leukemia, Hairy Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lymphoma, B-Cell, Marginal Zone/genetics , Splenic Neoplasms/genetics , Biopsy , Cell Line, Tumor , Chromosome Mapping , DNA, Neoplasm/genetics , Gene Dosage , Humans , In Situ Hybridization, Fluorescence , Leukemia, Hairy Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Lymphoma, B-Cell, Marginal Zone/epidemiology , Molecular Epidemiology , Splenic Neoplasms/epidemiology
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