Dansonka-Mieszkowska A, Ludwig A H, Kraszewska E, Kupryjańczyk J
Department of Molecular Pathology, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland.
Ann Hum Genet. 2006 Sep;70(Pt 5):594-604. doi: 10.1111/j.1469-1809.2006.00257.x.
The TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38%vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11%vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9%vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273(HIS) codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273(CYS) codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.
人类肿瘤中TP53基因突变谱显示出与肿瘤起源组织、致癌物暴露或分子背景相关的差异。我们比较了不同地理区域卵巢癌中的TP53突变；本研究基于从国际癌症研究机构数据库（R10，2005）中提取并验证的数据，以及我们对127例癌组织的研究结果。总共评估了873个突变。来自日本和韩国的肿瘤外显子7突变频率较高（38%对25%，p = 0.011），外显子8突变频率较低（11%对29%，p = 0.0003），高于西方国家的肿瘤；它们与挪威肿瘤差异尤为明显，挪威肿瘤外显子7突变比例最低（19%，p = 0.001），外显子8突变比例最高（37%，p < 0.0001）。TP53热点突变谱也存在差异。波兰肿瘤中的第三个热点是氨基酸（AA）176（替代突变占8.2%，其他国家为1.7%，p < 0.001），而英国肿瘤中的是AA 220（8.9%对2.3%，p < 0.001）。密码子273是挪威肿瘤中唯一明显的热点，而在波兰和亚洲肿瘤中很少发生突变。与其他数据相反，挪威肿瘤出现273（HIS）密码子（AA 273处突变占82%，p = 0.002），而英国肿瘤共有273（CYS）密码子（80%，p < 0.001）。按地理区域对卵巢癌中TP53基因突变进行进一步分析可能会提供更多见解。
