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Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene

Joachim Boucneau, Sofie De Schepper UGent, Marnik Vuylsteke UGent, Paul Van Hummelen, Jean Naeyaert and Jo Lambert UGent (2005) PIGMENT CELL RESEARCH. 18(4). p.285-299
abstract
One of the major primary features of the neurocutaneous genetic disorder Neurofibromatosis type 1 are the hyperpigmentary cafe-au-lait macules where disregulation of melanocyte biology is supposed to play a key etiopathogenic role. To gain better insight into the possible role of the tumor suppressor gene NF1, a transcriptomic microarray analysis was performed on human NF1 heterozygous (NF1(+/-)) melanocytes of a Neurofibromatosis type 1 patient and NF1 wild type (NF1(+/+)) melanocytes of a healthy control patient, both cultured from normally pigmented skin and hyperpigmented lesional cafe-au-lait skin. From the magnitude of gene effects, we found that gene expression was affected most strongly by genotype and less so by lesional type. A total of 137 genes had a significant twofold or more up- (72) or downregulated (65) expression in NF1(+/-) melanocytes compared with NF1(+/+) melanocytes. Melanocytes cultured from hyperpigmented cafe-au-lait skin showed 37 upregulated genes whereas only 14 were downregulated compared with normal skin melanocytes. In addition, significant genotype xlesional type interactions were observed for 465 genes. Differentially expressed genes were mainly involved in regulating cell proliferation and cell adhesion. A high number of transcription factor genes, among which a specific subset important in melanocyte lineage development, were downregulated in the cis-regulatory network governing the activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. Although the results presented have been obtained with a restricted number of patients (one NF1 patient and one control) and using cDNA microarrays that may limit their interpretation, the data nevertheless addresses for the first time the effect of a heterozygous NF1 gene on the expression of the human melanocyte transcriptome and has generated several interesting candidate genes helpful in elucidating the etiopathology of cafe-au-lait macules in NF1 patients.
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alternative title
Gene expression profiling of cultured human NF1 heterozygous (NF1(+/-)) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene
year
type
journalArticle (original)
publication status
published
subject
keyword
TUMOR-SUPPRESSOR, GROWTH-FACTOR, AU-LAIT MACULES, CREST-DERIVED MELANOCYTE, NEUROFIBROMATOSIS TYPE-1 GENE, microarray, DCT, melanocyte, cafe-au-lait macule, NF1, heterozygosity, HUMAN SKIN, PDZ PROTEIN, DNA-DAMAGE, IN-VIVO, TYROSINASE
journal title
PIGMENT CELL RESEARCH
Pigm. Cell. Res.
volume
18
issue
4
pages
285 - 299
Web of Science type
Article
Web of Science id
000230573900008
JCR category
CELL BIOLOGY
JCR impact factor
2.679 (2005)
JCR rank
70/152 (2005)
JCR quartile
2 (2005)
ISSN
0893-5785
DOI
10.1111/j.1600-0749.2005.00237.x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
328497
handle
http://hdl.handle.net/1854/LU-328497
date created
2006-03-24 10:27:00
date last changed
2016-12-19 15:41:34
@article{328497,
  abstract     = {One of the major primary features of the neurocutaneous genetic disorder Neurofibromatosis type 1 are the hyperpigmentary cafe-au-lait macules where disregulation of melanocyte biology is supposed to play a key etiopathogenic role. To gain better insight into the possible role of the tumor suppressor gene NF1, a transcriptomic microarray analysis was performed on human NF1 heterozygous (NF1(+/-)) melanocytes of a Neurofibromatosis type 1 patient and NF1 wild type (NF1(+/+)) melanocytes of a healthy control patient, both cultured from normally pigmented skin and hyperpigmented lesional cafe-au-lait skin. From the magnitude of gene effects, we found that gene expression was affected most strongly by genotype and less so by lesional type. A total of 137 genes had a significant twofold or more up- (72) or downregulated (65) expression in NF1(+/-) melanocytes compared with NF1(+/+) melanocytes. Melanocytes cultured from hyperpigmented cafe-au-lait skin showed 37 upregulated genes whereas only 14 were downregulated compared with normal skin melanocytes. In addition, significant genotype xlesional type interactions were observed for 465 genes. Differentially expressed genes were mainly involved in regulating cell proliferation and cell adhesion. A high number of transcription factor genes, among which a specific subset important in melanocyte lineage development, were downregulated in the cis-regulatory network governing the activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. Although the results presented have been obtained with a restricted number of patients (one NF1 patient and one control) and using cDNA microarrays that may limit their interpretation, the data nevertheless addresses for the first time the effect of a heterozygous NF1 gene on the expression of the human melanocyte transcriptome and has generated several interesting candidate genes helpful in elucidating the etiopathology of cafe-au-lait macules in NF1 patients.},
  author       = {Boucneau, Joachim and De Schepper, Sofie and Vuylsteke, Marnik and Van Hummelen, Paul and Naeyaert, Jean and Lambert, Jo},
  issn         = {0893-5785},
  journal      = {PIGMENT CELL RESEARCH},
  keyword      = {TUMOR-SUPPRESSOR,GROWTH-FACTOR,AU-LAIT MACULES,CREST-DERIVED MELANOCYTE,NEUROFIBROMATOSIS TYPE-1 GENE,microarray,DCT,melanocyte,cafe-au-lait macule,NF1,heterozygosity,HUMAN SKIN,PDZ PROTEIN,DNA-DAMAGE,IN-VIVO,TYROSINASE},
  language     = {eng},
  number       = {4},
  pages        = {285--299},
  title        = {Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene},
  url          = {http://dx.doi.org/10.1111/j.1600-0749.2005.00237.x},
  volume       = {18},
  year         = {2005},
}

Chicago
Boucneau, Joachim, Sofie De Schepper, Marnik Vuylsteke, Paul Van Hummelen, Jean-Marie Naeyaert, and Jo Lambert. 2005. “Gene Expression Profiling of Cultured Human NF1 Heterozygous (NF1+/-) Melanocytes Reveals Downregulation of a Transcriptional Cis-regulatory Network Mediating Activation of the Melanocyte-specific Dopachrome Tautomerase (DCT) Gene.” Pigment Cell Research 18 (4): 285–299.
APA
Boucneau, Joachim, De Schepper, S., Vuylsteke, M., Van Hummelen, P., Naeyaert, J.-M., & Lambert, J. (2005). Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. PIGMENT CELL RESEARCH, 18(4), 285–299.
Vancouver
1.
Boucneau J, De Schepper S, Vuylsteke M, Van Hummelen P, Naeyaert J-M, Lambert J. Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. PIGMENT CELL RESEARCH. 2005;18(4):285–99.
MLA
Boucneau, Joachim, Sofie De Schepper, Marnik Vuylsteke, et al. “Gene Expression Profiling of Cultured Human NF1 Heterozygous (NF1+/-) Melanocytes Reveals Downregulation of a Transcriptional Cis-regulatory Network Mediating Activation of the Melanocyte-specific Dopachrome Tautomerase (DCT) Gene.” PIGMENT CELL RESEARCH 18.4 (2005): 285–299. Print.