Krajewska Wanda M, Stawińska Magdalena, Bryś Magdalena, Młynarski Wojciech, Witas Henryk W, Okruszek Andrzej, Kiliańska Zofia M
Department of Cytobiochemistry, University of Łódź, Poland.
Med Sci Monit. 2003 May;9(5):BR188-91.
The gene encoding the tumor suppressor protein p53 is one of the most frequently mutated in human cancer. Over 8000 mutations of this gene have been identified. The spectrum of p53 mutations varies among tumor types. More than half of these mutations appear in three hotspot codons: 175, 248 and 273. The purpose of the present study was to evaluate the GgA transition in codon 175 of the p53 gene as a potential marker of colon cancer progression.
MATERIAL/METHODS: The prognostic significance of alterations in codon 175 exon 5 of p53 gene was studied in 32 patients with colorectal cancer. The ASA-PCR method was used to assess GgA (ArggHis) transition in codon 175.
The analyzed point mutation was identified in 56% of the tested cases of colorectal cancer. The frequency of codon 175 p53 gene mutation was found to increase with cancer aggressiveness. Screening for the studied point mutation in codon 175 showed no alteration in analyzed samples classified as Dukes' A stage, while variations were observed in 43%, 50% and 75% of the cases classified as Dukes' B, C, and D, respectively. In three cases the studied mutation was also found in some mucosal cells obtained from resectional borders.
The GgA transition in codon 175 of the p53 gene may be useful as a potential marker of colorectal cancer progression and as a means of evaluating the margins of surgical resection.
编码肿瘤抑制蛋白p53的基因是人类癌症中最常发生突变的基因之一。已鉴定出该基因的8000多种突变。p53突变谱在不同肿瘤类型中有所不同。这些突变中一半以上出现在三个热点密码子：175、248和273。本研究的目的是评估p53基因密码子175处的GgA转换作为结肠癌进展的潜在标志物。
材料/方法：在32例结直肠癌患者中研究了p53基因第5外显子密码子175改变的预后意义。采用ASA-PCR方法评估密码子175处的GgA（精氨酸→组氨酸）转换。
在56%的结直肠癌检测病例中鉴定出分析的点突变。发现密码子175 p53基因突变频率随癌症侵袭性增加而升高。对密码子175处研究的点突变进行筛查，结果显示，在归类为Dukes' A期的分析样本中未发现改变，而在分别归类为Dukes' B、C和D期的病例中观察到改变的比例分别为43%、50%和75%。在3例病例中，在从手术切缘获取的一些黏膜细胞中也发现了研究的突变。
p53基因密码子175处的GgA转换可能作为结直肠癌进展的潜在标志物以及评估手术切除切缘的一种手段。
