Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22
D J Demetrick1, H Zhang, D H Beach
1Cold Spring Harbor Laboratory, NY, USA. demetric@acs.ucalgary.ca
Abstract:
The human cdk2/cyclin A kinase complex is a key regulator of the events of S phase. This complex contains several proteins involved in regulating its catalytic activity, including one or more of the CKS proteins, which have recently been shown to inhibit the activation of the cdk2 kinase. To investigate whether the CKS genes may be altered in human neoplasia, we mapped the chromosome locations of CKS1 and CKS2 by fluorescence in situ hybridization (FISH). CKS1 was localized to 8q21, a locus that is seldom grossly altered in cancer. The localization of CKS2 to 9q22 places it very near to a putative tumour suppressor locus suggested to be responsible for susceptibility to the Basal Cell Nervus Syndrome (BCNS or Gorlin's syndrome) familial cancer disorder. Six fibroblast cell lines isolated from patients with BCNS were demonstrated by FISH to have both copies of CKS2 present. Partial sequencing of a genomic clone of CKS2 revealed that the open reading frame lies over three exons. Examination of the six cell lines by SSCP and PCR-based sequencing of the parts of the three exons coding for the full length protein demonstrated no consistent divergence from the reported cDNA sequence in any exon. It is unlikely that CKS2 is the BCNS tumour suppressor gene.
Insights
Researchers investigated the CKS genes
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The cdk2/cyclin A kinase complex regulates S phase.
- CKS proteins, including CKS1 and CKS2, modulate cdk2 kinase activity.
- Alterations in CKS genes are investigated for roles in human neoplasia.
Purpose of the Study:
- To map the chromosomal locations of CKS1 and CKS2.
- To investigate the potential involvement of CKS2 in Basal Cell Nervus Syndrome (BCNS).
Main Methods:
- Fluorescence in situ hybridization (FISH) for gene mapping.
- FISH to analyze CKS2 copy number in BCNS fibroblast cell lines.
- Partial sequencing and Single-Strand Conformation Polymorphism (SSCP) analysis of CKS2 exons.
Main Results:
- CKS1 was mapped to chromosome 8q21, a region rarely altered in cancer.
- CKS2 was localized to 9q22, near a putative tumor suppressor locus for BCNS.
- No consistent mutations or alterations in CKS2 were found in BCNS cell lines.
Conclusions:
- CKS1 is unlikely to be involved in common cancers due to its stable chromosomal location.
- CKS2 is unlikely to be the tumor suppressor gene responsible for BCNS susceptibility.
- Further research is needed to identify the specific genetic cause of BCNS.
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