Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor

Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conser...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1993-04, Vol.53 (7), p.1637-1641
Main Authors: THORLACIUS, S, BÖRRESEN, A.-L, EYFJÖRD, J. E
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Base Sequence
Biological and medical sciences
Breast Neoplasms - genetics
Chromosomes, Human, Pair 17
Conserved Sequence
DNA Mutational Analysis - methods
Exons - genetics
Female
Gene Deletion
Genes, p53 - genetics
Gynecology. Andrology. Obstetrics
Humans
Iceland
Mammary gland diseases
Medical sciences
Middle Aged
Molecular Sequence Data
Mutation - genetics
Polymerase Chain Reaction
Prognosis
Sensitivity and Specificity
Tumors
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Summary:Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001).
ISSN:0008-5472
1538-7445