Eyfjörd J E, Thorlacius S, Valgardsdottir R, Gretarsdottir S, Steinarsdottir M, Anamthawat-Jonsson K
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.
Acta Oncol. 1995;34(5):663-7. doi: 10.3109/02841869509094045.
TP53 abnormalities in breast carcinomas and inherited TP53 changes in breast cancer patients and in Li-Fraumeni-like families were looked for. Tumours were screened for mutations in the TP53 gene by means of the 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 staining. TP53 abnormalities in the tumours were examined in relation to genetic instability, clinical data and family history. Genetic instability was studied by detection of oncogene amplification, allelic loss, 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 chromosome 17. Chromosomal abnormalities were also significantly more common in tumours with TP53 abnormalities. Looking at clinical data we found significant association between TP53 abnormalities and poor prognosis.
研究人员对乳腺癌中的TP53异常以及乳腺癌患者和李-弗劳梅尼综合征样家族中的遗传性TP53变化进行了探寻。通过PCR-CDGE方法，随后进行PCR和直接测序，对肿瘤进行TP53基因突变筛查。通过比较正常DNA和肿瘤DNA，利用多态性标记确定等位基因缺失。通过免疫组织化学染色检查异常蛋白表达。结合基因不稳定性、临床数据和家族史，对肿瘤中的TP53异常进行了研究。通过检测癌基因扩增、等位基因缺失、核型分析和荧光原位杂交（FISH）来研究基因不稳定性。我们的研究表明，TP53异常与erbB2癌基因扩增以及17号染色体上的等位基因缺失显著相关。在有TP53异常的肿瘤中，染色体异常也明显更为常见。查看临床数据时，我们发现TP53异常与预后不良之间存在显著关联。
