A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines.
OBJECTIVE
Classical Hodgkin's lymphoma (cHL) is a common malignant lymphoma characterized by the presence of large, usually multinucleated malignant Hodgkin and Reed Sternberg (HRS) cells which are thought to be derived from germinal center B-cells. In cHL, the HRS cells constitute less than 1% of the tumor volume; consequently the profile of genetic aberrations in cHL is still poorly understood.


METHODS
In this study, we subjected four commonly used cHL cell lines to array comparative genomic hybridization (aCGH) in order to delineate known chromosomal aberrations in more detail and to search for small hitherto undetected genomic imbalances.


RESULTS
The aCGH profiles of the four cell lines tested confirmed the complex patterns of rearrangements previously demonstrated with M-FISH and chromosomal CGH (cCGH). Importantly, aCGH allowed a much more accurate delineation of imbalances as compared to previous studies performed at chromosomal level of resolution. Furthermore, we detected 35 hitherto undetected aberrations including a homozygous deletion of chromosomal region 15q26.2 in the cell line HDLM2 encompasing RGMA and CHD2 and an amplification of the STAT6 gene in cell line L1236 leading to STAT6 overexpression. Finally, in cell line KM-H2 we found a 2.35 Mb deletion at 16q12.1 putatively defining a small critical region for the recurrent 16q deletion in cHL. This region contains the CYLD gene, a known suppressor gene of the NF-mB pathway.


CONCLUSIONS
aCGH was performed on four cHL cell lines leading to the improved delineation of known chromosomal imbalances and the detection of 35 hitherto undetected aberrations. More specifically, our results highlight STAT6 as a potential transcriptional target and identified RGMA, CHD2 and CYLD as candidate tumor suppressors in cHL.
Feys
Tom
T
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Poppe
Bruce
B
De Preter
Katleen
K
Van Roy
Nadine
N
Verhasselt
Bruno
B
De Paepe
Pascale
P
De Paepe
Anne
A
Speleman
Frank
F
D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD