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

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 demonst rated increased levels of wild type p53 protein in skin fibroblasts (S F) of patients from heritable cancer syndrome, including familial aden omatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984,1986). Here, we furt her address the association between germline p53 alterations and genet ic predisposition to cancer in the SBLA syndrome and in FAP. DNA seque ncing 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 germl ine mutations in exons 5-9 of the p53 gene in SF from SBLA or FAP pati ents, including the Gardner variant. In addition, we observed no acqui red mutations in exons 5-9 of the p53 gene in benign tumors from FAP p atients. In conclusion, we found no association between germline p53 m utations and SBLA or FAP. How mechanisms that involve nonmutational ac tivation of the p53 protein might affect genetic predisposition to can cer remains to be established.