INK4a-ARF mutations in skin carcinomas from UV irradiated hairless mice.
To characterize further the role of the INK4a-ARF locus in the multistep process of skin carcinogenesis, we performed a mutational analysis of this locus in skin lesions from hairless mice either irradiated with UVB alone or with a solar simulator delivering UVA + B. INK4a-ARF mutations were present in five of 57 squamous cell carcinomas (9%), but no mutation was detected in precancerous lesions. All mutations were C:G > T:A transitions located at dipyrimidic sites, the hallmark of UVB mutagenesis. Three mutations affected only the p19(ARF) reading frame, whereas two mutations affected only the p16(INK4a) transcript. This study demonstrates for the first time UV-induced mutations of INK4a-ARF that occur in a small percentage in late stages skin tumors.
Soufir
N
N
Institut de Recherche sur la Peau, Inserm U 532, Hopital Saint-Louis, Paris, France.
Queille
S
S
Mollier
K
K
Roux
E
E
Sarasin
A
A
de Gruijl
F R
FR
Fourtanier
A M
AM
Daya-Grosjean
L
L
Basset-Seguin
N
N
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004249:DNA Damage / Q000528:radiation effects; D019942:Genes, p16; D051379:Mice; D008812:Mice, Hairless; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics; D011743:Pyrimidines / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011743:Pyrimidines; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53