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Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas.

Publication ,  Journal Article
Liu, FS; Kohler, MF; Marks, JR; Bast, RC; Boyd, J; Berchuck, A
Published in: Obstet Gynecol
January 1994

OBJECTIVE: To determine the frequency of mutation and overexpression of the p53 tumor suppressor gene in female genital tract sarcomas. METHODS: Immunostaining for p53 was performed in frozen sections of 46 ovarian and uterine sarcomas. Single-stranded conformation polymorphism analysis of exons 4-9 of the p53 gene was performed in 33 sarcomas. We performed DNA sequencing of the p53 gene in 22 cases in which we found p53 protein overexpression and/or shifted bands on single-stranded conformation polymorphism analysis. RESULTS: Overexpression of p53 was seen in 27 of 46 sarcomas (59%), including 26 of 41 (63%) mixed mesodermal tumors, one of four (25%) leiomyosarcomas, and zero of one endometrial stromal sarcoma. Among the 33 sarcomas subjected to molecular analysis, 21 demonstrated mutations in the p53 gene (64%). Eighteen cancers had a single mutation, whereas three cases showed two mutations in the p53 gene. There was one mutation in exon 4, seven mutations in exon 5, three mutations in exon 6, six mutations in exon 7, six mutations in exon 8, and one mutation in exon 9. With the exception of one microdeletion, which predicted a truncated protein product, all of the mutations were missense point mutations. All but one of the point mutations resulted in changes in the predicted amino acid sequence. There were 18 transition mutations (75%), five transversions (21%), and one deletion (4%). CONCLUSIONS: Mutation of the p53 tumor suppressor gene, with resultant overexpression of p53 protein, frequently occurs in ovarian and uterine sarcomas. Because most of the mutations are transitions, p53 mutations in these cancers likely arise from spontaneous errors in DNA synthesis and repair rather than from exposure to carcinogens.

Duke Scholars

Published In

Obstet Gynecol

ISSN

0029-7844

Publication Date

January 1994

Volume

83

Issue

1

Start / End Page

118 / 124

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Sarcoma
  • Polymorphism, Genetic
  • Ovarian Neoplasms
  • Obstetrics & Reproductive Medicine
  • Mutation
  • Middle Aged
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic
 

Citation

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MLA
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Liu, F. S., Kohler, M. F., Marks, J. R., Bast, R. C., Boyd, J., & Berchuck, A. (1994). Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas. Obstet Gynecol, 83(1), 118–124.
Liu, F. S., M. F. Kohler, J. R. Marks, R. C. Bast, J. Boyd, and A. Berchuck. “Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas.Obstet Gynecol 83, no. 1 (January 1994): 118–24.
Liu FS, Kohler MF, Marks JR, Bast RC, Boyd J, Berchuck A. Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas. Obstet Gynecol. 1994 Jan;83(1):118–24.
Liu, F. S., et al. “Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas.Obstet Gynecol, vol. 83, no. 1, Jan. 1994, pp. 118–24.
Liu FS, Kohler MF, Marks JR, Bast RC, Boyd J, Berchuck A. Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas. Obstet Gynecol. 1994 Jan;83(1):118–124.

Published In

Obstet Gynecol

ISSN

0029-7844

Publication Date

January 1994

Volume

83

Issue

1

Start / End Page

118 / 124

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Sarcoma
  • Polymorphism, Genetic
  • Ovarian Neoplasms
  • Obstetrics & Reproductive Medicine
  • Mutation
  • Middle Aged
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic