p53 Mutation analysis in breast tumors by a DNA microarray method.
نویسندگان
چکیده
The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study.
منابع مشابه
شناسایی جهش در اگزونهای پنج و شش ژن P53 در زنان مبتلا به سرطان پستان آذربایجان شرقی
Background and Objectives: Breast cancer (BC) is the most common invasive malignancy affecting women worldwide. The tumor-suppressor P53 gene (P53) is frequently mutated in breast tumors. To use P53 as a target for therapy, it is important to accurately assess p53 mutation status in tumor samples. Materials and Methods: A total of 102 tumor samples were collected from breast cancer patients ref...
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We have developed a simple and highly efficient method to detect deletions and insertions in the p53 gene. All 11 exons of the p53 gene were amplified along with a control sequence in four multiplex PCR reactions in the presence of fluorescein-labeled primers. The PCR products were resolved on an automated sequencing gel and the DNA fragments were detected by fluorescence. Using this method, we...
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ورودعنوان ژورنال:
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
دوره 15 1 شماره
صفحات -
تاریخ انتشار 2006