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A detailed inventory of DNA copy number alterations in four commonly used Hodgkin’s lymphoma cell lines

From the Centre for Medical Genetics (CMGG), Ghent University Hospital Ghent, Belgium (TF, BP, KDP, NVR, ADP, FS); Department of Clinical Chemistry, Microbiology and Immunology; Centre for Molecular Diagnostics, Ghent University Hospital, Ghent, Belgium (BV); Pathological Anatomy, AZ Sint Jan Bruges, Bruges, Belgium (PDP)

Correspondence: Frank Speleman, Centre for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: franki.speleman{at}ugent.be

Background and Objectives: 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.

Design and 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 multicolor fluorescence in situ hybridization and chromosomal CGH (cCGH). Importantly, aCGH allowed a much more accurate delineation of imbalances as compared to previous studies performed at a 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-B pathway.

Interpretation and 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.

Key words: Hodgkin’s lymphoma, cell line, array CGH.

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