Overexpression of a fish CDKN2 gene in a hereditary melanoma model

The fish genus Xiphophorus provides a vertebrate model useful in etiological studies of cancer. Hybrid fish can spontaneously develop melanomas deriving from the inheritance of melanistic pigment patterns and the simultaneous absence of proper genetic regulation. A cyclin-dependent kinase inhibitor...

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Published inCarcinogenesis (New York) Vol. 21; no. 4; pp. 599 - 605
Main Authors Kazianis, Steven, Coletta, Luis Della, Morizot, Donald C., Johnston, Dennis A., Osterndorff, Elizabeth A., Nairn, Rodney S.
Format Journal Article
LanguageEnglish
Published Oxford Oxford University Press 01.04.2000
Oxford Publishing Limited (England)
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Abstract The fish genus Xiphophorus provides a vertebrate model useful in etiological studies of cancer. Hybrid fish can spontaneously develop melanomas deriving from the inheritance of melanistic pigment patterns and the simultaneous absence of proper genetic regulation. A cyclin-dependent kinase inhibitor gene, termed CDKN2X, was mapped to a genomic region that is implicated in fish melanoma tumor suppression. The related human tumor suppressor locus CDKN2A (P16, INK4A, MTS1) is deleted, mutated or transcriptionally repressed through methylation of cytosine bases within the 5′ CpG island in a variety of neoplasms, including melanoma. The fish CDKN2X locus harbors a CpG island within its promoter and first exon, analogous in location to CpG islands in human CDKN2A and CDKN2B loci. The methylation state of individual CpG dinucleotides was investigated in genomic DNA derived from control tissues and melanomas within the CDKN2X 5′ CpG island. The studied genomic area was found to be virtually unmethylated in all tested tissues including melanomas. In addition, RNA expression studies of the fish CDKN2X locus revealed that it is significantly overexpressed in melanoma, in contrast to what has been reported for the human CDKN2A locus in melanoma. Such overexpression may be a consequence of the pronounced upregulation of the Xmrk-2 receptor tyrosine kinase oncogene reported in several Xiphophorus melanoma models.
AbstractList The fish genus Xiphophorus provides a vertebrate model useful in etiological studies of cancer. Hybrid fish can spontaneously develop melanomas deriving from the inheritance of melanistic pigment patterns and the simultaneous absence of proper genetic regulation. A cyclin-dependent kinase inhibitor gene, termed CDKN2X, was mapped to a genomic region that is implicated in fish melanoma tumor suppression. The related human tumor suppressor locus CDKN2A (P16, INK4A, MTS1) is deleted, mutated or transcriptionally repressed through methylation of cytosine bases within the 5′ CpG island in a variety of neoplasms, including melanoma. The fish CDKN2X locus harbors a CpG island within its promoter and first exon, analogous in location to CpG islands in human CDKN2A and CDKN2B loci. The methylation state of individual CpG dinucleotides was investigated in genomic DNA derived from control tissues and melanomas within the CDKN2X 5′ CpG island. The studied genomic area was found to be virtually unmethylated in all tested tissues including melanomas. In addition, RNA expression studies of the fish CDKN2X locus revealed that it is significantly overexpressed in melanoma, in contrast to what has been reported for the human CDKN2A locus in melanoma. Such overexpression may be a consequence of the pronounced upregulation of the Xmrk-2 receptor tyrosine kinase oncogene reported in several Xiphophorus melanoma models.
Author Coletta, Luis Della
Osterndorff, Elizabeth A.
Nairn, Rodney S.
Kazianis, Steven
Johnston, Dennis A.
Morizot, Donald C.
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  surname: Kazianis
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  givenname: Luis Della
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  givenname: Dennis A.
  surname: Johnston
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  organization: Department of Carcinogenesis, Science Park–Research Division, MD Anderson Cancer Center, University of Texas, PO Box 389, Smithville, TX 78957, USA
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  surname: Osterndorff
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  surname: Nairn
  fullname: Nairn, Rodney S.
  organization: Department of Carcinogenesis, Science Park–Research Division, MD Anderson Cancer Center, University of Texas, PO Box 389, Smithville, TX 78957, USA
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Issue 4
Keywords Animal model
Skin disease
Enzyme
Transcription promoter
Transferases
Spontaneous
Enzyme inhibitor
Gene overexpression
Malignant tumor
Gene expression
Hereditary
Carcinogenesis
CDKN2 gene
Vertebrata
Protein kinase
Animal
DNA
Pisces
Malignant melanoma
Cytosine
Methylation
Tumor suppressor gene
Phenotypic hybrid
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Snippet The fish genus Xiphophorus provides a vertebrate model useful in etiological studies of cancer. Hybrid fish can spontaneously develop melanomas deriving from...
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SubjectTerms Animal tumors. Experimental tumors
Animals
Biological and medical sciences
CDKN2A gene
CDKN2B gene
CDKN2X gene
CpG Islands
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyprinodontiformes
DNA Methylation
Female
Fish Diseases - genetics
Genes, Tumor Suppressor
INK4A gene
Medical sciences
Melanoma - genetics
Melanoma - veterinary
MTS1 gene
P16 gene
Promoter Regions, Genetic
RNA - analysis
Spontaneous animal tumors
Tumors
Xiphophorus
Xmrk-2 gene
Title Overexpression of a fish CDKN2 gene in a hereditary melanoma model
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https://www.ncbi.nlm.nih.gov/pubmed/10753192
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Volume 21
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