p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.
OBJECTIVE
The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness.


METHODS
We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing.


RESULTS
p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did.


CONCLUSIONS
Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.
Bolshakov
Svetlana
S
Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
Walker
Christopher M
CM
Strom
Sara S
SS
Selvan
Mano S
MS
Clayman
Gary L
GL
El-Naggar
Adel
A
Lippman
Scott M
SM
Kripke
Margaret L
ML
Ananthaswamy
Honnavara N
HN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002273:Carcinogens; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics*
D002273:Carcinogens; D003062:Codon