유방암에서 p53 암억제 유전자 변이에 대한 연구

초록

Breast cancer in women poses a problem, and it can be difficult at times to evaluate the possibility of cancer recurrence in early cancer. The probability of cancer recurrence in early breast cancer is not rare, so we studied the major role of gene mutation—especially p53—as an important prognostic factor to predict cancer recurrence. There is increasing evidence relating the development and progression of cancer to an accumulation of mutations at the genomic level. The most frequently mutated gene known to date in sporadic breast cancer appears to be the tumor suppressor gene **p53**. A mutation affecting the codon sequence of the p53 gene consequently leads to the loss of its negative growth control properties. Presently available results have indicated that mutations tend to cluster in a portion of the gene spanning codons 132 to 281 (corresponding to exons 5, 6, 7, 8, and 9), known to include four highly conserved blocks. These exons have been shown to comprise highly conserved sequences and are believed to be the target for over 90% of the acquired mutations in human cancer, with the majority localized in exons 5, 7, and 8. The author examined the p53 gene in genomic DNA samples from 46 primary breast cancer tissues fixed in formalin and embedded in paraffin, which were followed up for more than 36 months. Using the PCR-SSCP approach, the author analyzed exon 5 of p53 for detecting mutations by non-isotopic ethidium bromide staining, then analyzed the mutations by sequencing using the Sequenase PCR Product Sequencing Kit (USB, Product No. 70170, USA). Exon 5 of the p53 gene was amplified by PCR as 211 bp. Five of 46 (10.8%) mutations in exon 5 of the p53 gene were detected by the non-isotopic SSCP approach in PCR products. The mutations were analyzed by sequencing using the PCR product, and four of all were successfully sequenced. All of them were frameshift mutations, and all mutations were deletion of a single C base in codon 156 and a stop codon in codon 169. The other available Western results have shown missense mutations in G, C pairs. In conclusion, the sequencing analysis of mutant PCR products carefully proposes the probability that the mutant biology of breast cancer is different in Korean women compared to Western women. It is necessary to perform further study on mutations of other exons—2, 6, 7, 8, 9, and 11—of the p53 gene.

키워드