A low incidence of p53 mutations in pre-malignant lesions of the oral cavity from non-tobacco users.
To determine the incidence of p53 mutations in pre-malignant lesions of the oral cavity from individuals without prior history of tobacco use, we have analyzed the conserved regions of the p53 gene (exons 5-9) in archival oral cavity lesion specimens obtained from patients with varied tobacco use histories, by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. Twenty-six lesions were analyzed from 14 patients, with multiple lesions obtained from 8 patients. Six of these patients used tobacco, (3 being cigarette smokers, 1 ex-cigarette smoker, 1 moderate cigar smoker and 1 snuff chewer). The remaining 8 patients had no prior history of tobacco use. Thirteen of the pre-malignant lesions exhibited severe dysplasia, 9 exhibited moderate dysplasia and 4 exhibited mild dysplasia. Four of the 26 lesions exhibited p53 mutations, each being from a tobacco user. None of the 13 lesions from never-tobacco users exhibited p53 mutations. There was a significantly higher p53 mutation incidence in pre-malignant lesions from tobacco users (including ex-smokers) than in non-tobacco users as well as in cigarette smokers plus snuff chewers than in non-tobacco users. Two of the mutations were observed in lesions exhibiting severe dysplasia: 1 in a lesion exhibiting moderate dysplasia and 1 in a lesion exhibiting mild dysplasia. These data suggest that p53 mutation may be a very early event in oral cavity tumor progression and demonstrate that pre-malignant lesions obtained from non-tobacco users do not exhibit p53 mutations.
Lazarus
P
P
Division of Pathology and Toxicology, American Health Foundation, Valhalla, NY.
Garewal
H S
HS
Sciubba
J
J
Zwiebel
N
N
Calcagnotto
A
A
Fair
A
A
Schaefer
S
S
Richie
J P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007972:Leukoplakia, Oral / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking / Q000009:adverse effects*