p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis

Suzanne J. Baker, Antonette C. Preisinger, J. M. Jessup, Christos Paraskeva, Sanford Markowitz, J. K V Willson, Stanley Hamilton, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

Coordinate loss of one copy of the p53 gene and mutation of the remaining copy occur in colorectal carcinomas and in many other human malignancies. However, the prevalence of p53 gene mutations in carcinomas which maintain both parental copies of p53 has not previously been evaluated. Moreover, it is not known whether p53 gene mutations are limited to malignant tumors or whether they can also occur in benign neoplasms. To answer these questions, a total of 58 colorectal tumors have been examined; in each tumor, allelic losses were assessed using restriction fragment length polymorphisms and p53 gene mutations were assessed by sequencing cloned polymerase chain reaction products. The following conclusions emerged: (a) p53 gene mutations occurred but were relatively rare in adenomas, regardless of size and whether the adenomas were derived from patients with familial adenomatous polyposis; (b) In carcinomas as well as in adenomas, p53 gene mutations were infrequently observed in tumors which contain both copies of chromosome 17p (17% of 30 tumors), while tumors which lost one copy of chromosome 17p usually had a mutation in the remaining p53 allele (86% of 28 tumors); (c) p53 gene mutations were found at similar frequencies in primary tumor samples and in cell lines derived from tumors. These and other data suggest that the rate limiting step in p53 inactivation is point mutation and that once a mutation occurs, loss of the remaining wildtype allele rapidly follows. Both mutations and allelic losses generally occur near the transition from benign to malignant growth, and the p53 gene may play a causal role in this progression.

Original languageEnglish (US)
Pages (from-to)7717-7722
Number of pages6
JournalCancer Research
Volume50
Issue number23
StatePublished - Dec 1 1990

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p53 Genes
Carcinogenesis
Mutation
Neoplasms
Adenoma
Loss of Heterozygosity
Colorectal Neoplasms
Alleles
Carcinoma
Chromosomes, Human, Pair 17
Adenomatous Polyposis Coli
Tumor Cell Line
Point Mutation
Restriction Fragment Length Polymorphisms
Chromosomes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Baker, S. J., Preisinger, A. C., Jessup, J. M., Paraskeva, C., Markowitz, S., Willson, J. K. V., ... Vogelstein, B. (1990). p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Research, 50(23), 7717-7722.

p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. / Baker, Suzanne J.; Preisinger, Antonette C.; Jessup, J. M.; Paraskeva, Christos; Markowitz, Sanford; Willson, J. K V; Hamilton, Stanley; Vogelstein, Bert.

In: Cancer Research, Vol. 50, No. 23, 01.12.1990, p. 7717-7722.

Research output: Contribution to journalArticle

Baker, SJ, Preisinger, AC, Jessup, JM, Paraskeva, C, Markowitz, S, Willson, JKV, Hamilton, S & Vogelstein, B 1990, 'p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis', Cancer Research, vol. 50, no. 23, pp. 7717-7722.
Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JKV et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Research. 1990 Dec 1;50(23):7717-7722.
Baker, Suzanne J. ; Preisinger, Antonette C. ; Jessup, J. M. ; Paraskeva, Christos ; Markowitz, Sanford ; Willson, J. K V ; Hamilton, Stanley ; Vogelstein, Bert. / p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. In: Cancer Research. 1990 ; Vol. 50, No. 23. pp. 7717-7722.
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