TP53 ABNORMALITIES AND GENETIC INSTABILITY IN BREAST-CANCER

TP53 abnormalities in breast carcinomas and inherited TP53 changes in breast cancer patients and in Li-Fraumeni-like families were looked fo r, Tumours were screened for mutations in the TP53 gene by means of th e PCR-CDGE method followed by PCR and direct sequencing. Allelic loss was determined by polymorphic markers, by comparing normal and tumour DNA. Abnormal protein expression was examined by immunohistochemical s taining. TP53 abnormalities in the tumours were examined in relation t o genetic instability, clinical data and family history. Genetic insta bility was studied by detection of oncogene amplification, allelic los s, karyotype analysis and fluorescent in situ hybridization, FISH. Our studies showed that TP53 abnormalities were significantly associated with amplification of the erbB2 oncogene and allelic loss on chromosom e 17. Chromosomal abnormalities were also significantly more common in tumours with TP53 abnormalities. Looking at clinical data we found si gnificant association between TP53 abnormalities and poor prognosis.