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Updated: Aug 18, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma
W A Yeudall1, R Y Crawford, J F Ensley
1Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Abstract:
The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21. Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR). Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA. These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2-16 base pairs. In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour. The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event.
Insights
The MTS1/CDK4I gene, a tumor suppressor, is frequently altered in head and neck squamous cell carcinoma (HNSCC). Mutations in this gene, including deletions, were observed in HNSCC cell lines, suggesting inactivation is an in vivo event.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The MTS1/CDK4I gene, encoding a cyclin kinase inhibitor, is located on chromosome 9p21.
- This locus is a suspected site for a major tumor suppressor gene, potentially inactivated in head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To investigate the status of the MTS1/CDK4I gene in primary and metastatic HNSCC.
- To identify abnormalities in the MTS1/CDK4I gene locus and its transcript in HNSCC.
Main Methods:
- Utilized polymerase chain reaction (PCR) to examine the MTS1/CDK4I gene locus and transcript for abnormalities.
- Analyzed 14 HNSCC cell lines for deletions and alterations in p16 mRNA.
Main Results:
- Abnormalities in the MTS1/CDK4I gene were detected in all 14 HNSCC cell lines studied.
- These included loss of exons 1 and/or 2, and deletions (2-16 base pairs) in p16 mRNA transcripts, leading to frame shifts.
- Identical mutations were found in primary tumors and their corresponding metastases, indicating in vivo inactivation.
Conclusions:
- The MTS1/CDK4I gene is frequently altered in HNSCC.
- Mutations and deletions in the MTS1/CDK4I gene, leading to inactivation of p16 function, occur in vivo during tumor progression.
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