Abstract
The p15(INK4B), p16(INK4) and p18 genes are members of the gene family coding for inhibitors of cyclin-dependent kinases 4 and 6. p15(INK4B) and p16(INK4) are located at 9p21, a chromosomal region frequently deleted in many human neoplasms. To examine the role of these 3 genes in lung carcinogenesis, somatic mutations within the genes were analyzed by single-strand conformation polymorphism and DNA sequencing in 71 non-small-cell lung cancer (NSCLC) samples. Six somatic mutations in the p16(INK4) gene and 3 cases with a polymorphic allele were observed. Loss of heterozygosity in the p18 gene was found in 1 sample. We did not find any intragenic mutations in the p15(INK4B) or p18 genes. We conclude that p16(INK4) mutations play a role in the formation of some NSCLCs, whereas the involvement of p15(INK4B) and p18 is uncommon.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Carrier Proteins / genetics*
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Cell Cycle Proteins*
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p18
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DNA Mutational Analysis
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Enzyme Inhibitors / pharmacology
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Gene Deletion
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Heterozygote
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Humans
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Lung Neoplasms / genetics*
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Molecular Sequence Data
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Mutation*
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Polymerase Chain Reaction
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Polymorphism, Genetic
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Polymorphism, Single-Stranded Conformational
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Protein Kinase Inhibitors
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Tumor Suppressor Proteins*
Substances
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CDKN2B protein, human
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CDKN2C protein, human
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Carrier Proteins
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p18
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Enzyme Inhibitors
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Protein Kinase Inhibitors
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Tumor Suppressor Proteins