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Mutation of tumor suppressor gene p53 is frequently found in vulvar carcinoma cells

Authors
  • Hietanen, Sakari H.
  • Kurvinen, Kaisa
  • Syrjänen, Kari
  • Grénman, Seija
  • Carey, Thomas
  • McClatchey, Kenneth
  • Syrjänen, Stina
Type
Published Article
Journal
American Journal of Obstetrics and Gynecology
Publisher
Elsevier
Publication Date
Jan 01, 1995
Accepted Date
Mar 03, 1995
Volume
173
Issue
5
Pages
1477–1482
Identifiers
DOI: 10.1016/0002-9378(95)90636-3
Source
Elsevier
Keywords
License
Unknown

Abstract

OBJECTIVE: The purpose of this study was to evaluate the presence and type of mutations of the tumor suppressor gene p53 in squamous carcinoma cell lines of the vulva. STUDY DESIGN: Eight low-passage cell lines established from vulvar carcinoma were included in the analysis. Mutational analysis was restricted to exons 5 through 9 of the p53 gene, previously shown to have a high incidence of mutations. The sequences containing exons 5/6, 7, and 8/9 were amplified by polymerase chain reaction and screened with a single-strand conformation polymorphism technique on PhastSystem (Pharmacia Biotech, Uppsala, Sweden). Exons from samples showing mobility shifts in single-strand conformation polymorphism were sequenced by polymerase chain reaction direct sequencing. RESULTS: Five vulvar carcinoma cell lines showed abnormal electrophoretic mobility of exons 5/6, one of exons 6/9, and one of exon 7. Reduction to homozygosity was detected in four vulvar carcinoma cell lines. Missense mutatiosn were detected by sequence analysis in UM-SCV-2 (codon 171: GAG[Glu] → TAG[STOP]), UM-SCV-3 (hot spot codon 273: CGT[Arg] → TGT[Cys]), UM-SCV-4 (codon 151: CCC[Pro] → CAC[His]), UM-SCV-5 (codon 155: ACC[Thr] → ATC[Ile]), and UM-SCV-7 (codon 245: GGC[Gly] → AGC[Ser]). UM-SCV-3 also carried a missense mutation with no amine acid change (codon 314: TCC[Ser] → TCT[Ser]). UM-SCV-7 carried an additional base deletion at codon 249 (AGG → AG -), likely resulting in a frameshift in transcription and a truncated protei product. Four of the seven mutations were transitions, two were transversions, and one was a deletion. The presence of transitions suggests that at least a proportion of p53 mutations of these cancers may arise spontaneously without exogenous carcinogen exposure. UM-SCV-1A and UM-SCV-1B were derived from the primary tumor and pleural effusion of the same patient. UM-SCV-6 is a cell line that contains human papillomavirus 16. No mutations in these three cell lines were found by single-strand conformation polymorphism. CONCLUSIONS: On the basis of previous observations, loss of tumor suppressor p53 function either by mutation or human papillomavirus involvement is a frequent phenomenon in cervical carcinoma cells. It appears now that functional inactivation of p53 is associated with vulvar carcinoma cell lines, but mutations of the p53 gene are much more common in vulvar than in cervical carcinoma cell lines.

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