Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers.
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.
Rusin
M R
MR
Department of Tumor Biology, Institute of Oncology, Gliwice, Poland.
Okamoto
A
A
Chorazy
M
M
Czyzewski
K
K
Harasim
J
J
Spillare
E A
EA
Hagiwara
K
K
Hussain
S P
SP
Xiong
Y
Y
Demetrick
D J
DJ
Harris
C C
CC
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
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