Abstract
Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li- Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984, 1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP, DAN sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF form SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusions, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established.
| Original language | English |
|---|---|
| Pages (from-to) | 125-129 |
| Number of pages | 5 |
| Journal | Cancer Genetics and Cytogenetics |
| Volume | 90 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 1996 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Genetics
- Molecular Biology
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Absence of germline mutations in exons 5-9 of the p53 gene in patients with Li-Fraumeni-like (SBLA) and familial adenomatous polyposis heritable cancer syndromes. / Moore, Stephen K.; Zambrano, Nicola; Lynch, Henry T.; Lipkin, Martin; Kopelovich, Levy.
In: Cancer Genetics and Cytogenetics, Vol. 90, No. 2, 09.1996, p. 125-129.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Absence of germline mutations in exons 5-9 of the p53 gene in patients with Li-Fraumeni-like (SBLA) and familial adenomatous polyposis heritable cancer syndromes
AU - Moore, Stephen K.
AU - Zambrano, Nicola
AU - Lynch, Henry T.
AU - Lipkin, Martin
AU - Kopelovich, Levy
PY - 1996/9
Y1 - 1996/9
N2 - Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li- Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984, 1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP, DAN sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF form SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusions, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established.
AB - Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li- Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984, 1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP, DAN sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF form SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusions, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030248392&partnerID=8YFLogxK
U2 - 10.1016/S0165-4608(96)00072-6
DO - 10.1016/S0165-4608(96)00072-6
M3 - Article
VL - 90
SP - 125
EP - 129
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
SN - 0165-4608
IS - 2
ER -