The spectrum of p53 mutations in colorectal adenomas differs from that in colorectal carcinomas
The spectrum of p53 mutations in colorectal adenomas differs from that in colorectal carcinomas
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DOI：
10.1136/gut.50.6.834
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发表时间：
2002-06-01
期刊：
影响因子：
24.5
通讯作者：
Tomlinson, IPM
中科院分区：
文献类型：
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作者：
Hao, XP;Frayling, IM;Tomlinson, IPM
背景：P53基因突变在结直肠癌中常见，但在结直肠腺瘤中也有发现，虽然频率较低。目的：通过对选定的显微解剖细胞群体的分析，筛选出70例结直肠腺瘤中的P53等位基因缺失和点突变。结果：发现16例(22.8%)腺瘤存在等位基因缺失，其中11例(15.7%)存在P53突变。在轻度、中度和重度不典型增生的腺瘤中，突变或等位基因丢失的发生率分别为4.8%、16.7%和52.6%(p<；0.001)。发现了七种不同的突变，均为错义改变或基础缺失：一种(Thr150Arg)以前没有发现，三种(Gln144His，Gly245Arg和Glu285Gln)以前从未在结直肠癌中描述过。另外三个突变(Arg175Gly、DeltaPro190和Gly245Ser)已在结直肠癌中发现，这是最后一个常见的突变。腺瘤具有与癌症显著不同的p53突变谱，在基因中的位置和G-->；C/C-->；G改变的频率更高。结论：结合我们关于腺瘤的数据和已发表的数据，并与结直肠癌的突变谱相比较，我们认为一些p53突变的影响比其他突变更弱，因此更有可能在未进展为癌症的腺瘤中发现。
Background: p53 mutations are frequently observed in colorectal carcinomas but they have also been found in colorectal adenomas, although considerably less frequently.Aims: To explore p53 mutations in benign tumours, we have screened 70 colorectal adenomas for allelic loss at, and point mutations in, TP53 by analysis of selected microdissected cell populations.Results: Sixteen (22.8%) adenomas were found to have allelic loss, of which 11 (15.7%) had p53 mutations. In adenomas with mild, moderate, or severe dysplasia, mutation or allelic loss occurred in 4.8%, 16.7%, and 52.6%, respectively (p < 0.001). Seven different mutations were found, all missense changes or inframe deletions: one (Thr150Arg) has not been found before while three (Gln144His, Gly245Arg, and Glu285Gln) have not been described previously in colorectal tumours. The other three mutations (Arg175Gly, DeltaPro190, and Gly245Ser) have been found in colorectal carcinomas, the last commonly. Adenomas harboured a spectrum of p53 mutations which was significantly different from cancers as regards the position in the gene and a higher frequency of G-->C/C-->G changes.Conclusions: Combining our data on adenomas with data already published and in comparison with the spectrum of mutations in colorectal carcinomas, it is suggested that some p53 mutations have a weaker effect than others and are therefore more likely to be found in adenomas which have not progressed to carcinomas.