Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2.
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 1 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.
Joos
Stefan
S
German Cancer Research Center, H0700, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. s.joos@dkfz-heidelberg.de
Granzow
Martin
M
Holtgreve-Grez
Heidi
H
Siebert
Reiner
R
Harder
Lana
L
Martín-Subero
José I
JI
Wolf
Jürgen
J
Adamowicz
Martyna
M
Barth
Thomas F E
TF
Lichter
Peter
P
Jauch
Anna
A
D002869:Chromosome Aberrations; D002871:Chromosome Banding; D020223:Chromosome Painting; D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2; D007621:Karyotyping; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics*; D016615:Telomere; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2