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

Tom Feys, Bruce Poppe UGent, Katleen De Preter UGent, Nadine Van Roy UGent, Bruno Verhasselt UGent, Pascale De Paepe, Anne De Paepe UGent and Franki Speleman UGent (2007) HAEMATOLOGICA-THE HEMATOLOGY JOURNAL. 92(7). p.913-920
abstract
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-kappa 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IDENTIFICATION, FAMILY, DISEASE, EXPRESSION, ACTIVATION, TUMOR-SUPPRESSOR GENE, REED-STERNBERG CELLS, cell line, COMPARATIVE GENOMIC HYBRIDIZATION, NF-KAPPA-B, hodgkin's lymphoma, array CGH, AMPLIFICATION
journal title
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
Haematol-Hematol. J.
volume
92
issue
7
pages
913 - 920
Web of Science type
Article
Web of Science id
000247703300008
JCR category
HEMATOLOGY
JCR impact factor
5.516 (2007)
JCR rank
9/61 (2007)
JCR quartile
1 (2007)
ISSN
0390-6078
DOI
10.3324/haematol.11073
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
376639
handle
http://hdl.handle.net/1854/LU-376639
date created
2007-09-12 13:02:00
date last changed
2015-06-17 10:44:40
@article{376639,
  abstract     = {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-kappa 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.},
  author       = {Feys, Tom and Poppe, Bruce and De Preter, Katleen and Van Roy, Nadine and Verhasselt, Bruno and De Paepe, Pascale and De Paepe, Anne and Speleman, Franki},
  issn         = {0390-6078},
  journal      = {HAEMATOLOGICA-THE HEMATOLOGY JOURNAL},
  keyword      = {IDENTIFICATION,FAMILY,DISEASE,EXPRESSION,ACTIVATION,TUMOR-SUPPRESSOR GENE,REED-STERNBERG CELLS,cell line,COMPARATIVE GENOMIC HYBRIDIZATION,NF-KAPPA-B,hodgkin's lymphoma,array CGH,AMPLIFICATION},
  language     = {eng},
  number       = {7},
  pages        = {913--920},
  title        = {A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines},
  url          = {http://dx.doi.org/10.3324/haematol.11073},
  volume       = {92},
  year         = {2007},
}

Chicago
Feys, Tom, Bruce Poppe, Katleen De Preter, Nadine Van Roy, Bruno Verhasselt, Pascale De Paepe, Anne De Paepe, and Franki Speleman. 2007. “A Detailed Inventory of DNA Copy Number Alterations in Four Commonly Used Hodgkin’s Lymphoma Cell Lines.” Haematologica-the Hematology Journal 92 (7): 913–920.
APA
Feys, Tom, Poppe, B., De Preter, K., Van Roy, N., Verhasselt, B., De Paepe, P., De Paepe, A., et al. (2007). A detailed inventory of DNA copy number alterations in four commonly used Hodgkin’s lymphoma cell lines. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 92(7), 913–920.
Vancouver
1.
Feys T, Poppe B, De Preter K, Van Roy N, Verhasselt B, De Paepe P, et al. A detailed inventory of DNA copy number alterations in four commonly used Hodgkin’s lymphoma cell lines. HAEMATOLOGICA-THE HEMATOLOGY JOURNAL. 2007;92(7):913–20.
MLA
Feys, Tom, Bruce Poppe, Katleen De Preter, et al. “A Detailed Inventory of DNA Copy Number Alterations in Four Commonly Used Hodgkin’s Lymphoma Cell Lines.” HAEMATOLOGICA-THE HEMATOLOGY JOURNAL 92.7 (2007): 913–920. Print.