title: Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers.
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.
authors.affiliation: Department of Tumor Biology, Institute of Oncology, Gliwice, Poland.
authors.forename: M R
authors.initials: MR
authors.lastname: Rusin
authors.forename: A
authors.initials: A
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Chorazy
authors.forename: K
authors.initials: K
authors.lastname: Czyzewski
authors.forename: J
authors.initials: J
authors.lastname: Harasim
authors.forename: E A
authors.initials: EA
authors.lastname: Spillare
authors.forename: K
authors.initials: K
authors.lastname: Hagiwara
authors.forename: S P
authors.initials: SP
authors.lastname: Hussain
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: D J
authors.initials: DJ
authors.lastname: Demetrick
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins
chemical_list: C493966:CDKN2B protein, human; C493971:CDKN2C protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins