Absence of significant germ line p53 mutations in ovarian cancer patients.
Germ line mutations of the p53 gene have been described in the Li-Fraumeni Cancer Family Syndrome and occur in patients with multifocal gliomas, particularly those with a history of a metachronous cancer or a family history of cancer. p53 dysfunction is often associated with ovarian cancer. Patients with ovarian carcinoma frequently develop synchronous or metachronous cancers and may have a family history of this or related cancers. Thus, we hypothesized that germ line p53 mutations might be associated with a significant proportion of ovarian cancers. Germ line DNA isolated from peripheral leukocytes of 73 patients with ovarian carcinoma was screened for p53 sequence abnormalities utilizing single-strand conformation polymorphism analysis and direct PCR sequencing techniques. As many as 40% of this cohort of ovarian cancer patients from 67 families may represent familial phenotypes. Synchronous and metachronous cancers occurred in 19% of the cohort. Only two intron-based polymorphisms were found. Neither has been previously reported. One of these, in intron 6, occurred in three unrelated patients all of whom had a history of metachronous breast cancer. A polymorphism in intron 10 occurred in a patient with synchronous endometrial cancer. No classic germ line mutations of p53 were found.
Buller
R E
RE
Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Skilling
J S
JS
Kaliszewski
S
S
Niemann
T
T
Anderson
B
B
D001483:Base Sequence; D015331:Cohort Studies; D005091:Exons; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008499:Medical Records; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D015335:Molecular Probes; D016159:Tumor Suppressor Protein p53