Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2

被引:115
作者
Joos, S
Granzow, M
Holtgreve-Grez, H
Siebert, R
Harder, L
Martín-Subero, JI
Wolf, J
Adamowicz, M
Barth, TFE
Lichter, P
Jauch, A
机构
[1] Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany
[2] Univ Heidelberg, Inst Humangenet, Heidelberg, Germany
[3] Christian Albrechts Univ Kiel Klinikum, Inst Humangenet, Kiel, Germany
[4] Univ Cologne, Cologne, Germany
[5] Univ Ulm Klinikum, Abt Pathol, Ulm, Germany
关键词
Hodgkin's lymphoma; cytogenetic aberration; telomeric segment translocation; REL; JAK2;
D O I
10.1002/ijc.10845
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Four Hodgkin's lymphoma cell lines (KM-H2, HDLM-2, L428, L1236) were analyzed for cytogenetic aberrations, applying multiplex fluorescence in situ hybridization, chromosome banding and comparative genomic hybridization. Each line was characterized by a highly heterogeneous pattern of karyotypic changes with a large spectrum of different translocated chromosomes (range 22-57). A recurrent finding in all cell lines was the presence of chromosomal rearrangements of the short arm of chromosome 2 involving the REL oncogene locus. Furthermore, multiple translocated copies of telomeric chromosomal segments were frequently detected. This resulted in a copy number increase of putative oncogenes, e.g., JAK2 (9p24) in 3 cell lines, FGFR3 (4p16) and CCND2 (12p13) in 2 cell lines as well as MYC (8q24) in I cell line. Our data confirm previous cytogenetic results from primary Hodgkin's tumors suggesting an important pathogenic role of REL and JAK2 in this disease. In addition, they provide evidence for a novel cytogenetic pathomechanism leading to increased copy numbers of putative oncogenes from terminal chromosomal regions, most probably in the course of chromosomal stabilization by telomeric capture. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:489 / 495
页数:7
相关论文
共 33 条
[1]   CONSTRUCTION AND CHARACTERIZATION OF A YEAST ARTIFICIAL CHROMOSOME LIBRARY CONTAINING 7 HAPLOID HUMAN GENOME EQUIVALENTS [J].
ALBERTSEN, HM ;
ABDERRAHIM, H ;
CANN, HM ;
DAUSSET, J ;
LEPASLIER, D ;
COHEN, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (11) :4256-4260
[2]   Cytogenetics of Hodgkin's disease [J].
Atkin, NB .
CYTOGENETICS AND CELL GENETICS, 1998, 80 (1-4) :23-27
[3]   Constitutive nuclear factor-κB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells [J].
Bargou, RC ;
Emmerich, F ;
Krappmann, D ;
Bommert, K ;
Mapara, MY ;
Arnold, W ;
Royer, HD ;
Grinstein, E ;
Greiner, A ;
Scheidereit, C ;
Dörken, B .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (12) :2961-2969
[4]   Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3 [J].
Chesi, M ;
Nardini, E ;
Brents, LA ;
Schrock, E ;
Ried, T ;
Kuehl, WM ;
Bergsagel, PL .
NATURE GENETICS, 1997, 16 (03) :260-264
[5]   Genomic organization of human JAK2 and mutation analysis of its JH2-domain in leukemia [J].
Cools, J ;
Peeters, P ;
Voet, T ;
Aventin, A ;
Meeucci, C ;
Grandchamp, B ;
Marynen, P .
CYTOGENETICS AND CELL GENETICS, 1999, 85 (3-4) :260-266
[6]  
Drexler H. G., 2000, LEUKEMIA LYMPHOMA CE
[7]   QUANTITATIVE-ANALYSIS OF COMPARATIVE GENOMIC HYBRIDIZATION [J].
DUMANOIR, S ;
SCHROCK, E ;
BENTZ, M ;
SPEICHER, MR ;
JOOS, S ;
RIED, T ;
LICHTER, P ;
CREMER, T .
CYTOMETRY, 1995, 19 (01) :27-41
[8]   An optimized, fully automated system for fast and accurate identification of chromosomal rearrangements by multiplex-FISH (M-FISH) [J].
Eils, R ;
Uhrig, S ;
Saracoglu, K ;
Sätzler, K ;
Bolzer, A ;
Petersen, I ;
Chassery, JM ;
Ganser, M ;
Speicher, MR .
CYTOGENETICS AND CELL GENETICS, 1998, 82 (3-4) :160-171
[9]  
Fonatsch C, 1999, HODGKIN'S DISEASE, P213
[10]   Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances [J].
Franke, S ;
Wlodarska, I ;
Maes, B ;
Vandenberghe, P ;
Delabie, J ;
Hagemeijer, A ;
De Wolf-Peeters, C .
BLOOD, 2001, 97 (06) :1845-1853