Abstract
Based on the high incidence of loss of het-rozgosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern analysis, immunoprecipitation, and nucleotide sequeneing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10657-10661 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 88 |
| Issue number | 23 |
| State | Published - 1991 |
| Externally published | Yes |
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Keywords
- Gene mutation
- Multiplex PCR
- Protein expression
ASJC Scopus subject areas
- General
- Genetics
Cite this
Mutations in p53 as potential molecular markers for human breast cancer. / Runnebaum, Ingo B.; Nagarajan, Mahalakshmi; Bowman, Marianne; Soto, Darya; Sukumar, Saraswati.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 23, 1991, p. 10657-10661.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutations in p53 as potential molecular markers for human breast cancer
AU - Runnebaum, Ingo B.
AU - Nagarajan, Mahalakshmi
AU - Bowman, Marianne
AU - Soto, Darya
AU - Sukumar, Saraswati
PY - 1991
Y1 - 1991
N2 - Based on the high incidence of loss of het-rozgosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern analysis, immunoprecipitation, and nucleotide sequeneing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.
AB - Based on the high incidence of loss of het-rozgosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern analysis, immunoprecipitation, and nucleotide sequeneing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.
KW - Gene mutation
KW - Multiplex PCR
KW - Protein expression
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M3 - Article
C2 - 1961733
AN - SCOPUS:0025719004
VL - 88
SP - 10657
EP - 10661
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 23
ER -