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CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23

Evi Michels UGent, Jasmien Hoebeeck UGent, Katleen De Preter UGent, Alexander Schramm, Bénédicte Brichard, Anne De Paepe UGent, Angelika Eggert, Genevieve Laureys UGent, Jo Vandesompele UGent and Franki Speleman UGent (2008) BMC CANCER. 8.
abstract
Background: Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes. Methods: To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing. Results: Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines. Conclusion: Our study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of CADM1 in neuroblastoma development and to investigate the possibility of CADM1 haploinsufficiency in neuroblastoma.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
TUMORS, TSLC1, EXPRESSION, LUNG-CANCER, PROBE DATABASE, CHROMOSOME 11Q, ALLELIC DELETION, TIME PCR PRIMER, COMPARATIVE GENOMIC HYBRIDIZATION, CELL-ADHESION MOLECULE
journal title
BMC CANCER
BMC Cancer
volume
8
article_number
173
pages
9 pages
Web of Science type
Article
Web of Science id
000257251200001
JCR category
ONCOLOGY
JCR impact factor
3.087 (2008)
JCR rank
59/141 (2008)
JCR quartile
2 (2008)
ISSN
1471-2407
DOI
10.1186/1471-2407-8-173
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
432234
handle
http://hdl.handle.net/1854/LU-432234
date created
2008-10-23 10:50:00
date last changed
2010-08-09 11:06:35
@article{432234,
  abstract     = {Background: Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes.
Methods: To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing.
Results: Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines.
Conclusion: Our study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of CADM1 in neuroblastoma development and to investigate the possibility of CADM1 haploinsufficiency in neuroblastoma.},
  articleno    = {173},
  author       = {Michels, Evi and Hoebeeck, Jasmien and De Preter, Katleen and Schramm, Alexander and Brichard, B{\'e}n{\'e}dicte and De Paepe, Anne and Eggert, Angelika and Laureys, Genevieve and Vandesompele, Jo and Speleman, Franki},
  issn         = {1471-2407},
  journal      = {BMC CANCER},
  keyword      = {TUMORS,TSLC1,EXPRESSION,LUNG-CANCER,PROBE DATABASE,CHROMOSOME 11Q,ALLELIC DELETION,TIME PCR PRIMER,COMPARATIVE GENOMIC HYBRIDIZATION,CELL-ADHESION MOLECULE},
  language     = {eng},
  pages        = {9},
  title        = {CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23},
  url          = {http://dx.doi.org/10.1186/1471-2407-8-173},
  volume       = {8},
  year         = {2008},
}

Chicago
Michels, Evi, Jasmien Hoebeeck, Katleen De Preter, Alexander Schramm, Bénédicte Brichard, Anne De Paepe, Angelika Eggert, Genevieve Laureys, Jo Vandesompele, and Franki Speleman. 2008. “CADM1 Is a Strong Neuroblastoma Candidate Gene That Maps Within a 3.72 Mb Critical Region of Loss on 11q23.” Bmc Cancer 8.
APA
Michels, E., Hoebeeck, J., De Preter, K., Schramm, A., Brichard, B., De Paepe, A., Eggert, A., et al. (2008). CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC CANCER, 8.
Vancouver
1.
Michels E, Hoebeeck J, De Preter K, Schramm A, Brichard B, De Paepe A, et al. CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC CANCER. 2008;8.
MLA
Michels, Evi, Jasmien Hoebeeck, Katleen De Preter, et al. “CADM1 Is a Strong Neuroblastoma Candidate Gene That Maps Within a 3.72 Mb Critical Region of Loss on 11q23.” BMC CANCER 8 (2008): n. pag. Print.