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Mutations in the p53 tumor suppressor gene in human cutaneous squamous cell carcinomas
Author(s) -
Pierceall William E.,
Mukhopadhyay Tapas,
Goldberg Leonard H.,
Ananthaswamy Honnavara N.
Publication year - 1991
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940040606
Subject(s) - biology , exon , tumor suppressor gene , gene , microbiology and biotechnology , single strand conformation polymorphism , cancer research , mutation , transition (genetics) , suppressor , silent mutation , transversion , genetics , carcinogenesis , missense mutation
In this study, we analyzed 10 human squamous cell carcinomas (SCCs) for alterations in the p53 tumor suppressor gene in exons 4 through 9 by single‐strand conformation polymorphism (SSCP) analysis. We found that 2 of 10 SCCs displayed unusual SSC Pallelesat exon 7 of the p53 gene. Subsequent cloning and sequencing of PCR‐amplified exon 7 DNA from these two tumors revealed that one had a G→A transition at the first position of codon 244, predicting a glycine‐to‐serine amino acid change, while the other tumor exhibited a G→T base change at the second nucleotide of codon 248, predicting an arginine‐to‐leucine substitution. Because the mutations in the p53 tumor suppressor gene in both tumors were located opposite potential pyrimidine dimer sites (C‐C), it is consistent with these mutations having been induced by the ultraviolet radiation present in sunlight. These studies demonstrate that inactivation of the p53 tumor suppressor gene, as well as activation of ras oncogenes, may be involved in the pathogenesis of some human skin cancers.