Strand specificity and absence of hot spots for p53 mutations in ultraviolet B-induced skin tumors of XPA-deficient mice

Seiji Takeuchi, Yoshimichi Nakatsu, Hironobu Nakane, Hiroaki Murai, Seiichi Hirota, Yukihiko Kitamura, Akihiko Okuyama, Kiyoji Tanaka

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34 Citations (Scopus)

Abstract

We examined the spectrum of p53 mutations found in 40 UV-induced skin tumors of xeroderma pigmentosum group A gene (XPA)-deficient mice. p53 mutations were detected in 48% of the tumors. Nearly all of the mutations were induced at dipyrimidine sites. Ninety-three % of the mutations were G ·C→A·T transitions at dipyrimidine sites, including tandem transitions (CC→TT), which are the hallmark of the UVB-induced mutation. Seventy-two % of the mutations at dipyrimidine sites could be ascribed to damage on the transcribed strand. In addition, no evident mutational hot spots were detected. This is in contrast to the UVB-induced skin tumors of normal mice, in which 92% of p53 mutations occurred as a result of DNA damage on the nontranscribed strand, and clear hot spots were observed. Thus, XPA-deficient mice showed significant mutation features that might be characteristic of the absence of nucleotide excision repair and may provide a good animal model for the analysis of the high incidence of skin cancer in xeroderma pigmentosum group A patients.

Original languageEnglish
Pages (from-to)641-646
Number of pages6
JournalCancer Research
Volume58
Issue number4
Publication statusPublished - Feb 15 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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