Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas

Kenneth Buetow, Val C. Sheffield, Minghua Zhu, Tianlun Zhou, F. U Min Shen, Okio Hino, Moyra Smith, Brian J. Mcmahon, Anne P. Lanier, W. Thomas London, Allan G. Redeker, Sugantha Govindarajan

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Recent studies of the p53 tumor suppressor locus (designated TP53) in primary hepatocellular carcinoma (PHC) have identified a high frequency of codon 249 mutations. Due to the geographic location from which the samples were obtained and the substitution observed, the mutation was suggested to be attributable to aflatoxin B1 (AFB1) exposure. To determine the generality of this phenomenon, we have examined PHC tissues from 107 geographically and ethnically diverse sources. The frequency of p53 gene mutations was evaluated by using PCR/restriction-digest methods, GC-clamp (G+C-rich sequence) denaturing gradient gel electrophoresis, and DNA sequencing. The mutation rate observed in tumors from high-AFB1-exposure regions (25%) was more than double the rate observed in low-exposure regions (12%) but lower than the 50% frequency previously reported. Codon 249 mutations occurred at a much lower frequency than previously reported (2 of 107 samples examined). These results suggest that changes in DNA encoding p53 may not represent primary oncogenic effects but instead represent genetic changes related to tumor progression. High AFB1 levels may facilitate the generation of these progressional changes, but not by inducing a specific p53 gene mutation at codon 249 as previously reported.

Original languageEnglish (US)
Pages (from-to)9622-9626
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number20
StatePublished - Oct 15 1992
Externally publishedYes

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Mutation Rate
Hepatocellular Carcinoma
Aflatoxin B1
Mutation
Codon
p53 Genes
Geographic Locations
Neoplasms
Denaturing Gradient Gel Electrophoresis
DNA Sequence Analysis
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas. / Buetow, Kenneth; Sheffield, Val C.; Zhu, Minghua; Zhou, Tianlun; Shen, F. U Min; Hino, Okio; Smith, Moyra; Mcmahon, Brian J.; Lanier, Anne P.; Thomas London, W.; Redeker, Allan G.; Govindarajan, Sugantha.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 20, 15.10.1992, p. 9622-9626.

Research output: Contribution to journalArticle

Buetow, K, Sheffield, VC, Zhu, M, Zhou, T, Shen, FUM, Hino, O, Smith, M, Mcmahon, BJ, Lanier, AP, Thomas London, W, Redeker, AG & Govindarajan, S 1992, 'Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas', Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 20, pp. 9622-9626.
Buetow, Kenneth ; Sheffield, Val C. ; Zhu, Minghua ; Zhou, Tianlun ; Shen, F. U Min ; Hino, Okio ; Smith, Moyra ; Mcmahon, Brian J. ; Lanier, Anne P. ; Thomas London, W. ; Redeker, Allan G. ; Govindarajan, Sugantha. / Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 20. pp. 9622-9626.
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abstract = "Recent studies of the p53 tumor suppressor locus (designated TP53) in primary hepatocellular carcinoma (PHC) have identified a high frequency of codon 249 mutations. Due to the geographic location from which the samples were obtained and the substitution observed, the mutation was suggested to be attributable to aflatoxin B1 (AFB1) exposure. To determine the generality of this phenomenon, we have examined PHC tissues from 107 geographically and ethnically diverse sources. The frequency of p53 gene mutations was evaluated by using PCR/restriction-digest methods, GC-clamp (G+C-rich sequence) denaturing gradient gel electrophoresis, and DNA sequencing. The mutation rate observed in tumors from high-AFB1-exposure regions (25{\%}) was more than double the rate observed in low-exposure regions (12{\%}) but lower than the 50{\%} frequency previously reported. Codon 249 mutations occurred at a much lower frequency than previously reported (2 of 107 samples examined). These results suggest that changes in DNA encoding p53 may not represent primary oncogenic effects but instead represent genetic changes related to tumor progression. High AFB1 levels may facilitate the generation of these progressional changes, but not by inducing a specific p53 gene mutation at codon 249 as previously reported.",
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